PREFACE
The purpose of this essay is to show that even the origin of life is not blind speculation when it comes to science. There are real models for its natural origin that are open to experimental testing, and therefore to a degree of verification, in the lab.
No one is claiming that these models and tests are conclusive. But they exist, and they are testable.
INTRODUCTION
For all things in the universe, mainstream science assumes that their origins derive from natural processes of some kind. (An exception is made for the universe, the origin of which, involves more philosophical reasoning and speculating than it does scientific.). However, life itself exists in the universe. Therefore it is assumed that it had a naturalistic origin.
Most agree that the process behind this origin is poorly understood, if understood at all. Nevertheless, speculations and hypotheses are open to scientific testing, simply because the basis for them is placed within the natural world. That is, given a hypothesis involving matter, energy, and natural law, then the hypothesis will be, in principle, open to experimental testing.
In a recent issue of Nature, part of a hypothesis regarding the natural origin of life is firmed up, thanks to some interesting experimental work from researchers (1).
This essay is a brief description of that work.
WARNING
I think I got this one more or less correct. It did not try to dwell too much on terms like C10 membranes (4:1:1 decanoic acid
OH:GMD) which I think is simply a kind of membrane made up of 3 types of organic molecule in a ratio of 4 to 1 to 1. But you see what I mean? Nevertheless, there will be errors in my understanding. Those errors are mine.
TWO COMPETING HYPOTHESES
There are two hypotheses dealing with how the first organisms obtained their energy and food. One is the autotrophic model. The other is the heterotrophic model.
The autotrophic model, perhaps the more complex of the two, posits that early proto organisms were able to generate their own food and energy by harnessing simple metabolic reactions that had already come together inside the first simple cells. The heterotrophic model proposes that the proto organisms obtained their food and energy from external sources. They simply gobbled up what was already there.
A serious problem with the heterotrophic model has been with the cellular membranes of those primitive cells. Our cells are like bags of chemicals, captured inside a double layered film of fatty organic matter. This double layered film is very impermeable to large and electrically charged molecules crossing its boundary. Permeability is something that would be needed in the heterotrophic model if the first cells were to get their food from external sources. Our cells get around this problem by having all kinds of molecules sitting in the enclosing membrane, molecules which capture food on the outside, allowing or causing it to pass through. Presumably these little machines would not yet have arisen in the early environment, at least not with respect to the heterotrophic model.
So the researchers decided to test proto cells with membranes made up of molecules similar to those used by our cells and see what happens when the proto cells were placed in a sea of biologically important molecules. Placing the proto cells inside a sea of nutrients to find out what happens was an important step forward because until now, experimental effort had been directed towards finding out what happens to biological molecules already inside primitive cells. Naturally then, much of the experiment I describe here deals with membranes and their permeability to biological molecules. The different membrane molecules used in the experiments were plausible candidates for a pre-biotic earth.
The upshot of this experiment reported in Nature was that the scientists strengthened the case for a heterotrophic origin of life.
THE TEST
The researchers allowed proto-cells to naturally form in various solutions. Those cells (vesicles) had enclosing membranes made of molecules related to, but not the same as those in modern cell membranes. They wanted to see if the properties of these membrane molecules (shape, charge, size, etc) made any difference to a membranes ability to allow a simple sugar, ribose (from RNA), to cross it.
These membranes could be made of a single kind of molecule (e.g. myristoleic acid) or various mixtures of molecules (e.g. myristoleic acid and farnesol). All molecules were deemed to have been likely on the early earth.
Into the solution with its vesicles, they dissolved ribose and were able to show that some membranes did allow ribose to pass, by an increased factor of 4. Making the membranes more disordered by incorporating other molecules, increased the permeability by factors of 10 and even 17.
Permeability increase was one thing. But would the vesicles hold the sugar, once taken in? Observations showed that short stands of sugars were both taken in and retained indefinitely inside vesicles with membranes made of the molecules just mentioned. This indicated that the membranes suffered no significant rupture caused by the sugar chains passing through, nor that the membranes had large pores, both of which would allow the sugars to flow back out, once inside a vesicle.
The next question was the ability of the membranes to allow other components of RNA and DNA (called nucleotide nutrients) to cross. This was done by encapsulating these molecules inside the vesicles and measuring the fraction that leaked out. A property of these molecules is that they carry high negative charges due to a surplus of electrons. The high charges (and/or large molecule sizes) was shown to be a factor in preventing leakage of these molecules, that is, the membranes are largely impermeable to charged molecules or molecules of large size. By adding positively charged magnesium ions, the net negative charge on the molecules was reduced, allowing the leakage to increase slightly
The tests described above, revealed the need to reduce the charge on nutrient molecules to enhance their ability to cross a membrane boundary. So the researchers attempted their measurements on nucleotides which had been activated (primed for reaction with other molecules) by imidazole, a ring structured organic compound. The activated nucleotides had less charge than the non-activated ones and ended up showing similar abilities to the ribose sugar to cross membrane barriers. That is, if the membrane was composed of a single molecular type, then the activated nucleotides showed much less ability to cross the boundary than if the membrane was composed of two or more specific molecules. Nevertheless, even those single molecule type membranes were significantly permeable.
They think they understand how the membrane molecules transfer the nucleotides from outside to inside the vesicle. Forces between the nucleotides and the heads and tails of the membrane molecules, cause the membrane molecules to flip the nucleotides over from the outside to the inside of a membrane layer. These forces are caused by what are called polar charges. Such charges result from an uneven distribution of electrons around a molecule, causing net negative and net positive charges on the molecular surface.
Following the assessment of membrane types to permeability of molecules all of which are believed to have been important prebiotically, the researchers turned their attention to a more thorough test of a prebiotic cell model. The question was whether these vesicles could take up activated nucleotides from the outside, and use them to engage in template copying reactions on the inside.
Previous work had demonstrated that a variety of copying reactions could occur inside vesicles. Therefore the next step would be to show that the vesicles were capable of taking in nutrients from the outside and use them in these copying reactions. This ability to take in nutrients and use them is requirement of the heterotrophic model. By template copying it is meant that the proto-cell could engage in the beginnings of a primitive kind of reproduction namely copying its RNA. In this case, the copying was by lengthening the RNA chain. Unfortunately though, there is no known general reaction in which genetic molecules copy themselves without the aid of enzymes. However, there is one kind of genetic molecule called an oligo dC DNA which can do this, and it does it rather well. The molecule is a short strand of cytosine bases linked together. So the researchers cobbled together this molecule and tested it inside two kinds of vesicles. Adding activated nucleotide to the solution surrounding the vesicles, they were able to demonstrate that this nucleotide could be taken up and used inside the vesicle in a simple template copying reaction.
As expected, vesicles with membranes made up of the same organic molecules found in modern cell walls, did not do this. That is, these modern membrane walls remained impermeable to the external molecules needed for template copying.
THEIR CONCLUSION
The authors concluded their paper by pointing out that this set of experiments have a direct bearing on the autotrophic and heterotrophic models of early proto-cells. Until now, that membrane problem had appeared to be a major argument against the heterotrophic model. More so, these experiments argue against the autotrophic concept because internally generated metabolites would leak out (presumably because such products tend to have high residual electronic charges?). Remember, the autotrophic model relies on the concept of primitive/simple reaction networks coming together to generate the food and energy for the cell. The claim then, is that the food molecules generated by these reactions would leak out, causing the overall reaction chains to fail.
In this set of experiments however, the researchers showed the possibility of food being taken in, due to its low electronic charge, and not leaking back out, but rather being used in primitive replication reactions inside the cell.
As the authors conclude:-
Regards, Roland
The purpose of this essay is to show that even the origin of life is not blind speculation when it comes to science. There are real models for its natural origin that are open to experimental testing, and therefore to a degree of verification, in the lab.
No one is claiming that these models and tests are conclusive. But they exist, and they are testable.
INTRODUCTION
For all things in the universe, mainstream science assumes that their origins derive from natural processes of some kind. (An exception is made for the universe, the origin of which, involves more philosophical reasoning and speculating than it does scientific.). However, life itself exists in the universe. Therefore it is assumed that it had a naturalistic origin.
Most agree that the process behind this origin is poorly understood, if understood at all. Nevertheless, speculations and hypotheses are open to scientific testing, simply because the basis for them is placed within the natural world. That is, given a hypothesis involving matter, energy, and natural law, then the hypothesis will be, in principle, open to experimental testing.
In a recent issue of Nature, part of a hypothesis regarding the natural origin of life is firmed up, thanks to some interesting experimental work from researchers (1).
This essay is a brief description of that work.
WARNING
I think I got this one more or less correct. It did not try to dwell too much on terms like C10 membranes (4:1:1 decanoic acid
TWO COMPETING HYPOTHESES
There are two hypotheses dealing with how the first organisms obtained their energy and food. One is the autotrophic model. The other is the heterotrophic model.
The autotrophic model, perhaps the more complex of the two, posits that early proto organisms were able to generate their own food and energy by harnessing simple metabolic reactions that had already come together inside the first simple cells. The heterotrophic model proposes that the proto organisms obtained their food and energy from external sources. They simply gobbled up what was already there.
A serious problem with the heterotrophic model has been with the cellular membranes of those primitive cells. Our cells are like bags of chemicals, captured inside a double layered film of fatty organic matter. This double layered film is very impermeable to large and electrically charged molecules crossing its boundary. Permeability is something that would be needed in the heterotrophic model if the first cells were to get their food from external sources. Our cells get around this problem by having all kinds of molecules sitting in the enclosing membrane, molecules which capture food on the outside, allowing or causing it to pass through. Presumably these little machines would not yet have arisen in the early environment, at least not with respect to the heterotrophic model.
So the researchers decided to test proto cells with membranes made up of molecules similar to those used by our cells and see what happens when the proto cells were placed in a sea of biologically important molecules. Placing the proto cells inside a sea of nutrients to find out what happens was an important step forward because until now, experimental effort had been directed towards finding out what happens to biological molecules already inside primitive cells. Naturally then, much of the experiment I describe here deals with membranes and their permeability to biological molecules. The different membrane molecules used in the experiments were plausible candidates for a pre-biotic earth.
The upshot of this experiment reported in Nature was that the scientists strengthened the case for a heterotrophic origin of life.
THE TEST
The researchers allowed proto-cells to naturally form in various solutions. Those cells (vesicles) had enclosing membranes made of molecules related to, but not the same as those in modern cell membranes. They wanted to see if the properties of these membrane molecules (shape, charge, size, etc) made any difference to a membranes ability to allow a simple sugar, ribose (from RNA), to cross it.
These membranes could be made of a single kind of molecule (e.g. myristoleic acid) or various mixtures of molecules (e.g. myristoleic acid and farnesol). All molecules were deemed to have been likely on the early earth.
Into the solution with its vesicles, they dissolved ribose and were able to show that some membranes did allow ribose to pass, by an increased factor of 4. Making the membranes more disordered by incorporating other molecules, increased the permeability by factors of 10 and even 17.
Permeability increase was one thing. But would the vesicles hold the sugar, once taken in? Observations showed that short stands of sugars were both taken in and retained indefinitely inside vesicles with membranes made of the molecules just mentioned. This indicated that the membranes suffered no significant rupture caused by the sugar chains passing through, nor that the membranes had large pores, both of which would allow the sugars to flow back out, once inside a vesicle.
The next question was the ability of the membranes to allow other components of RNA and DNA (called nucleotide nutrients) to cross. This was done by encapsulating these molecules inside the vesicles and measuring the fraction that leaked out. A property of these molecules is that they carry high negative charges due to a surplus of electrons. The high charges (and/or large molecule sizes) was shown to be a factor in preventing leakage of these molecules, that is, the membranes are largely impermeable to charged molecules or molecules of large size. By adding positively charged magnesium ions, the net negative charge on the molecules was reduced, allowing the leakage to increase slightly
The tests described above, revealed the need to reduce the charge on nutrient molecules to enhance their ability to cross a membrane boundary. So the researchers attempted their measurements on nucleotides which had been activated (primed for reaction with other molecules) by imidazole, a ring structured organic compound. The activated nucleotides had less charge than the non-activated ones and ended up showing similar abilities to the ribose sugar to cross membrane barriers. That is, if the membrane was composed of a single molecular type, then the activated nucleotides showed much less ability to cross the boundary than if the membrane was composed of two or more specific molecules. Nevertheless, even those single molecule type membranes were significantly permeable.
They think they understand how the membrane molecules transfer the nucleotides from outside to inside the vesicle. Forces between the nucleotides and the heads and tails of the membrane molecules, cause the membrane molecules to flip the nucleotides over from the outside to the inside of a membrane layer. These forces are caused by what are called polar charges. Such charges result from an uneven distribution of electrons around a molecule, causing net negative and net positive charges on the molecular surface.
Following the assessment of membrane types to permeability of molecules all of which are believed to have been important prebiotically, the researchers turned their attention to a more thorough test of a prebiotic cell model. The question was whether these vesicles could take up activated nucleotides from the outside, and use them to engage in template copying reactions on the inside.
Previous work had demonstrated that a variety of copying reactions could occur inside vesicles. Therefore the next step would be to show that the vesicles were capable of taking in nutrients from the outside and use them in these copying reactions. This ability to take in nutrients and use them is requirement of the heterotrophic model. By template copying it is meant that the proto-cell could engage in the beginnings of a primitive kind of reproduction namely copying its RNA. In this case, the copying was by lengthening the RNA chain. Unfortunately though, there is no known general reaction in which genetic molecules copy themselves without the aid of enzymes. However, there is one kind of genetic molecule called an oligo dC DNA which can do this, and it does it rather well. The molecule is a short strand of cytosine bases linked together. So the researchers cobbled together this molecule and tested it inside two kinds of vesicles. Adding activated nucleotide to the solution surrounding the vesicles, they were able to demonstrate that this nucleotide could be taken up and used inside the vesicle in a simple template copying reaction.
As expected, vesicles with membranes made up of the same organic molecules found in modern cell walls, did not do this. That is, these modern membrane walls remained impermeable to the external molecules needed for template copying.
THEIR CONCLUSION
The authors concluded their paper by pointing out that this set of experiments have a direct bearing on the autotrophic and heterotrophic models of early proto-cells. Until now, that membrane problem had appeared to be a major argument against the heterotrophic model. More so, these experiments argue against the autotrophic concept because internally generated metabolites would leak out (presumably because such products tend to have high residual electronic charges?). Remember, the autotrophic model relies on the concept of primitive/simple reaction networks coming together to generate the food and energy for the cell. The claim then, is that the food molecules generated by these reactions would leak out, causing the overall reaction chains to fail.
In this set of experiments however, the researchers showed the possibility of food being taken in, due to its low electronic charge, and not leaking back out, but rather being used in primitive replication reactions inside the cell.
As the authors conclude:-
Nature ref (1) said:Although both models must overcome numerous conceptual difficulties related to the origin of complex molecular building blocks, the heterotrophic model was thought to face the additional difficulty of importing polar and even charged molecules across a bilayer lipid membrane. We have shown that fatty-acid-based membranes allow a simple protocells to acquire critical nutrients, while retaining polymerized nucleic acids indefinitely. Our results therefore support the idea that extremely simple heterotrophic protcells could have emerged within a prebiotic environment rich in complex nutrients.
Regards, Roland