Synthesis of a Single-cell Organism

[CycloWizard]

I drove about 700 miles yesterday, so I had a lot of time to think about nothing in particular. I'm not terribly familiar with research in biology, so maybe this has already been done. I was wondering if anyone has successfully created a single-cell organism from scratch (read: chemical precursors). Basically, can we construct the simplest organism from its most basic components without using nature's building blocks? Can I start with a pile of chemicals and create a very simple organism?

 

[jagec]

Nope, not even close.

 

[CycloWizard]

Originally posted by: jagec
Nope, not even close.

That's what I though, but I wanted to be sure. My next question is then how does biology explain the beginning of life? Was it simply a random occurrence when everything happened to be at the perfect conditions? If so, what did the first organism eat? These may be stupid questions, but if someone could humor me, it would be greatly appreciated.

edit: I guess what I'm driving at is: does biology yet have an explanation for how life began? I'm having a hard time getting my hands around this apparent discontinuity.

 

[sundev]

Well I wouldn't say "not even close", because there have been successful attempts at creating "cells" with membranes and limited internal structure, but they weren't alive. You can read about it here: http://news.bbc.co.uk/1/hi/sci/tech/1142840.stm

Also, it has been shown that amino acids and certain organic polymers can spontaneously form.. on of prevailing theories is that given enough time (a few hundred million years is plenty), the molecules that spontaneously form more complex ones (RNA or even DNA), which eventually forms life. Or something like that.

 

[cquark]

Originally posted by: CycloWizard

Originally posted by: jagec
Nope, not even close.

That's what I though, but I wanted to be sure. My next question is then how does biology explain the beginning of life? Was it simply a random occurrence when everything happened to be at the perfect conditions? If so, what did the first organism eat? These may be stupid questions, but if someone could humor me, it would be greatly appreciated.

edit: I guess what I'm driving at is: does biology yet have an explanation for how life began? I'm having a hard time getting my hands around this apparent discontinuity.

There are many hyptheses about abiogenesis, but none has sufficient experimental evidence yet to become a theory. The precursors of life, like amino acids, are abundant in the cosmos, and we can produce chemical replicators that evolve in the test tube. The big debate today is over how we got from chemical replicators to protocells, with three major types of hypotheses::

[*]Genes First models, like the RNA world hypothesis
[*]Metabolism First models, like the iron-sulfur world hypothesis, thioesters, and so forth
[*]Hybrid Models, that combine aspects

It's an exciting area of current research, with new papers and experiments being advanced all the time. You can find plenty of information about all of the above hypotheses and much more on Google.

As for your other questions, it certainly wasn't a random occurrence, and the first organisms likely derived their energy (ate, in your terms) from chemical sources like organisms on ocean floor sulfur vents do today.

 

[gururu]

we will never be able to recreate the origin of life. I know it is a strong statement, but we have about as much chance as monkeys to do it. Either, the answers will come with a more intelligent, capable form of life, or it will be brought to us by aliens.

all organisms do is shuttle and trade electrons, just like the components of any chemical reaction. organisms are nothing but extraordinarily complex chemical reactions. If life persists on earth for millions/billions of more years, organisms and the cells they are composed of will probably be even far more complex.

 

[wacki]

The answers in this thread so far have been next to horrible.

Every chemical in the cell can be made synthetically. The toughest challenge so far is separating the left handed chemicals from the right handed chemicals. To know what those are, just look at your hands. You have 2 hands and they are exactly the same. But one is left handed and the other is right handed. This happens in chemical synthesis all the time. Organisms on earth are right handed. (We found left handed proteins on a meteorite which means there may be alien life?!?!) After that problem is solved the only remaining question left is why? Why go through the massive amounts of work required to build a 100% synthetic cell when you can just "Frankenstein" it. Do you have any idea how much work it would take to make all those chemicals by hand? And then to get them all in the right spot? Why do that??? The "Frankenstein" technique by the way has now become routine. It's easy!

 

[unipidity]

The why is pretty obvious to me. I like the clay-abiogenisis best... just because its so whimsically weird. Yay for science based on whimsy.

Its about as philosophically consitent and physics based on 'beauty'.

 

[silverpig]

<jim carrey> It was ME!!!!! </jim carrey>

😀

 

[Gibsons]

One thing to consider is how limited we are (or want to be depending on the limits of the argument) in our ability to synthesize larger molecules. If we're strictly limiting ourselves to 'from scratch' chemical synthesis, we can only make DNA molecules about 100 or so nucleotides long, when we'd need something like 100,000 or so (number subject to debate). Then there's the question of getting big proteins made and properly folded. Chemical synthesis of proteins is notoriously ineffecient, worse than nucleic acids. But if you allow cloning and growing of DNA in bacteria, or using cellular extracts to make your proteins, things get somewhat easier.

Anyway, I think the way to approach it would be to try to copy a small genome from some bacteria (maybe adding some bits to help get things started before replication could begin), put that into some synthetic lipid bilayers along with a big protein mix... there are a lot of reasons why this approach might not work though.

 

[Gannon]

Scientists barely have a grasp on how animals speciate let alone abiogenesis, it will be centuries before they get it all figured out, you're dealing with trillion+ cellular organisms and hundreds of millions if not billions of celled organs as well. Not to mention there are a tonne of life forms we have not discovered on this planet that need to be studied before we have something truly substantial. Most of our knowledge is limited by the tools we have to investigate what goes on at the chemical level and cells are machines they synthetically self-manufacture themselves, cellular division is more akin to auto manufacturing then it is to simple 2nd order kinetic reactions. It is very highly controlled and many critical steps in the manufacture are carefully isolated from their environments. They are not even close nor will they be for centuries to come because advances in basic sciences and instrument technology effect all sciences and have profound implications as the data is seen in higher resolution then before. Right now many of the things we look at are extremely difficult to look at without destroying / effecting what we're trying to look at.

 

[Taejin]

You guys should try majoring in biochemistry before you start conjecturing.

In terms of theoretical synthesis, a single celled organism could be possible by scientists, but the physical limitations right now are great enough (and funding not large enough).

If you learn more about biology and the structure of cells, it should be fairly obvious that people are close to the "creation of life". There is a few areas that scientists still haven't fully uncovered.

Also, wacki seems like he has a clue about what he's talking about. The whole right-handed/left-handed thing he's talking about refers to centers of chirality in chemical compounds. Biochemicals have naturally evolved to be left-handed, rather than right-handed.

Also, you have to remember that those "simple cells" are highly automated machinery. You will not find 99% D-sugars and 1% L-sugars. It will be 100% D-sugars.

If you learn anything about refining/synthesis of chemicals you will find out that expense goes up exponentially up the purer an item gets. For example:

95% ethanol is relatively cheap. If you do repeated distillations, 95.5% is the highest concentration of ethanol you can get. However, 100% ethanol distillation takes further refinement/more expensive techniques, and is about 40x more expensive than 95.5% ethanol.

In a setting like simple cellular structures, where the chemical compounds we are dealing with ARE NOT simple 3 chain alcohols (ethanol is CH3-CH2-OH) but more along the lines of compounds from 30 to 300+ carbons, the expense and headache is simply not worth it.



Dunno if it makes any sense to you guys, but synthesis of pure compounds in order to do something like this is not worth it.

 

[Gibsons]

most of the basic building blocks - amino acids, nucleotides, simple carbohydrates, some lipids - are readily available (not even that expensive) at 99% + purity. While expense can go up with incremental increases in purity, most molecules don't suffer the azeotrope problem seen with ethanol and water. 99% purity is plenty good enough for RNA transcription, protein synthesis, etc.

The real issues here (imo) are getting enough correctly folded proteins ready at the start, achieving necessary levels of compartmentation (maybe not so important for a simple enough organism, hard to say), getting the right initial concentrations (cells are something like 30% protein - ever tried to make a solution of 30% protein?), and somehow getting the relative level transcripion of all the genes something close to the right level before things really get started. And faithfully creating a 100kb DNA molecule is no small task, even if you 'cheat' and grow it up in bacteria.

 

[gururu]

Taejin[/i]

You guys should try majoring in biochemistry before you start conjecturing.

try a PhD with a lifetime of laboratory experience in biochem.

In terms of theoretical synthesis, a single celled organism could be possible by scientists, but the physical limitations right now are great enough (and funding not large enough).

If you learn more about biology and the structure of cells, it should be fairly obvious that people are close to the "creation of life". There is a few areas that scientists still haven't fully uncovered.

the conjecture in these statements is strong. the reality is that this is so far from the truth.

Also, wacki seems like he has a clue about what he's talking about. The whole right-handed/left-handed thing he's talking about refers to centers of chirality in chemical compounds. Biochemicals have naturally evolved to be left-handed, rather than right-handed.

Also, you have to remember that those "simple cells" are highly automated machinery. You will not find 99% D-sugars and 1% L-sugars. It will be 100% D-sugars.

what does this have to do with our ability to create life?

If you learn anything about refining/synthesis of chemicals you will find out that expense goes up exponentially up the purer an item gets. For example:

exponentially is a gross exaggeration and quite the generalization.

95% ethanol is relatively cheap. If you do repeated distillations, 95.5% is the highest concentration of ethanol you can get. However, 100% ethanol distillation takes further refinement/more expensive techniques, and is about 40x more expensive than 95.5% ethanol.

In a setting like simple cellular structures, where the chemical compounds we are dealing with ARE NOT simple 3 chain alcohols (ethanol is CH3-CH2-OH) but more along the lines of compounds from 30 to 300+ carbons, the expense and headache is simply not worth it.

Dunno if it makes any sense to you guys, but synthesis of pure compounds in order to do something like this is not worth it.

saying we don't do something because it is not worth it doesn't mean it can be done.

 

[CycloWizard]

Originally posted by: wacki
...

It's more useful as a thought experiment than an actual chemistry/biology experiment. The thought process surrounding this is what intrigues me rather than the actual experiments, though I am very interested in whether or not we could create life from scratch. Point being (I guess) that it could help give a more concrete definition to life, which seems like a pretty tricky thing to put your finger on, at least philosophically. I was thinking that if we, with all our vaunted knowledge (sic), cannot build the molecule from scratch, what is the probability of it occurring randomly then propagating to such an amazing extent over a finite time scale?

 

[Taejin]

Originally posted by: gururu
Taejin[/i]

You guys should try majoring in biochemistry before you start conjecturing.

try a PhD with a lifetime of laboratory experience in biochem.

In terms of theoretical synthesis, a single celled organism could be possible by scientists, but the physical limitations right now are great enough (and funding not large enough).

If you learn more about biology and the structure of cells, it should be fairly obvious that people are close to the "creation of life". There is a few areas that scientists still haven't fully uncovered.

the conjecture in these statements is strong. the reality is that this is so far from the truth.

Also, wacki seems like he has a clue about what he's talking about. The whole right-handed/left-handed thing he's talking about refers to centers of chirality in chemical compounds. Biochemicals have naturally evolved to be left-handed, rather than right-handed.

Also, you have to remember that those "simple cells" are highly automated machinery. You will not find 99% D-sugars and 1% L-sugars. It will be 100% D-sugars.

what does this have to do with our ability to create life?

If you learn anything about refining/synthesis of chemicals you will find out that expense goes up exponentially up the purer an item gets. For example:

exponentially is a gross exaggeration and quite the generalization.

95% ethanol is relatively cheap. If you do repeated distillations, 95.5% is the highest concentration of ethanol you can get. However, 100% ethanol distillation takes further refinement/more expensive techniques, and is about 40x more expensive than 95.5% ethanol.

In a setting like simple cellular structures, where the chemical compounds we are dealing with ARE NOT simple 3 chain alcohols (ethanol is CH3-CH2-OH) but more along the lines of compounds from 30 to 300+ carbons, the expense and headache is simply not worth it.

Dunno if it makes any sense to you guys, but synthesis of pure compounds in order to do something like this is not worth it.

saying we don't do something because it is not worth it doesn't mean it can be done.

Sorry, all your rebuttals reek of bullshit to me.

I'm a junior in college, majoring in biochemistry and biochemical engineering. I study hard and I do well in my classes - I think I do know what I am talking about, unless my professors have been lying to me all this time.

Please prop up your statements with more than the ineffectual "no you're wrong". I am curious to see your real reasoning.

And the bolding is annoying, but if you must bold your important answers, I suppose I'll have to bear it.

 

[Taejin]

Also for clarification:

I wasn't claiming that scientists knew exactly how "life" came about - or rather a higher organization of molecules.

I was just saying given attention and a bit of effort by the scientific community, creation of an extremely simple single celled organism would be possible. Extremely simple. Present-day bacteria would be Einstein compared to the retard the scientists would produce.

 

[cquark]

Originally posted by: CycloWizard
I was thinking that if we, with all our vaunted knowledge (sic), cannot build the molecule from scratch, what is the probability of it occurring randomly then propagating to such an amazing extent over a finite time scale?

By molecule, I assume you mean cell, as we can construct molecules from atoms. I wouldn't rate our knowledge in molecular biology very highly, as it's an extremely new science. After all, we've only read (sequenced) a few genomes and that only in the last few years, so it's a bit early in our development to be writing new ones from scratch.

Finally, once again, life didn't come about randomly. There's a strong and obvious difference between selection and randomness. We can demonstrate replication and selection with molecules alone, as I pointed out above. Selection in the form of genetic algorithms and similar methods has become an effective means of solving certain types of problems that we can't solve directly through our intelligence and knowledge, so it shouldn't be underrated.

 

[gururu]

Originally posted by: Taejin

Sorry, all your rebuttals reek of bullshit to me.

I'm a junior in college, majoring in biochemistry and biochemical engineering. I study hard and I do well in my classes - I think I do know what I am talking about, unless my professors have been lying to me all this time.

Please prop up your statements with more than the ineffectual "no you're wrong". I am curious to see your real reasoning.

And the bolding is annoying, but if you must bold your important answers, I suppose I'll have to bear it.

no need to cuss. when you say something like:

You guys should try majoring in biochemistry before you start conjecturing.

you set yourself up for some flaming. particularly because your answers didn't do much more than conjecture and I didn't interpret your answers as coming from someone with first hand experience or extensive knowledge in the biological sciences. sorry, undergrad just doesn't cut it, and you'll realize this if you pursue a higher degree.
Also, when you say something like this:

I suppose I'll have to bear it.

and admit you are a mere junior in college, I sense a high arrogance/ knowledge ratio, which probably means arguing will be impossible.

the simple facts are these:

1) everyone has the right to conjecture regardless of their knowledge. And you aren't high enough on the totem pole to tell others below you to shut up. I'm much higher on the pole than you and I think everyones answers count.

2) your assessment that there are only a FEW areas of the creation of life that are not yet understood reeks of ignorance. How do you come to this?

3) you get on this discussion of molecular handedness and don't make any attempt to tie it in to the question at hand: Can a single cell organism be synthesized?

4) using the term 'exponential' to describe costs is ridiculous. also, to say that costs and interests are prohibitive towards the appropriate experimental research required to undertake such a task is wrong. the reason that funding in this area is weak is because NOONE has come up with a good plan on how to do it. That is, there is NO faith that it can be done. and these judgements are made by scientists that know what they are doing.

anyways, keep the cussing out, I'm still interested in hearing your views.

 

[jhu]

Originally posted by: CycloWizard

Originally posted by: wacki
...

It's more useful as a thought experiment than an actual chemistry/biology experiment. The thought process surrounding this is what intrigues me rather than the actual experiments, though I am very interested in whether or not we could create life from scratch. Point being (I guess) that it could help give a more concrete definition to life, which seems like a pretty tricky thing to put your finger on, at least philosophically. I was thinking that if we, with all our vaunted knowledge (sic), cannot build the molecule from scratch, what is the probability of it occurring randomly then propagating to such an amazing extent over a finite time scale?

want a bigger philosophical headache? do the entire project digitally using a massive supercomputer. now, given that those digital cells do the same things a real cell does but in a virtual world, do those digital cells constitute life?

 

[Kibbo]

Originally posted by: gururu

If you learn anything about refining/synthesis of chemicals you will find out that expense goes up exponentially up the purer an item gets. For example:

exponentially is a gross exaggeration and quite the generalization.

Don't know nothing about biochem, but exponentially would mesh well with the economic theory of returns diminishing at a logorithmic rate. Of course, in practical application, where you are on the curve can vary widely, and the actual marginal rate of diminishment (is that a word?) may not neccessairily seem logorithmic.

 

[Taejin]

Originally posted by: gururu

Originally posted by: Taejin

Sorry, all your rebuttals reek of bullshit to me.

I'm a junior in college, majoring in biochemistry and biochemical engineering. I study hard and I do well in my classes - I think I do know what I am talking about, unless my professors have been lying to me all this time.

Please prop up your statements with more than the ineffectual "no you're wrong". I am curious to see your real reasoning.

And the bolding is annoying, but if you must bold your important answers, I suppose I'll have to bear it.

no need to cuss. when you say something like:

Well I apologize for my use of the word 'bullshit', since it seems to offend you. I wasn't attempting to cuss per se, I was just saying your post smacked of something less than knowledge, period.

You guys should try majoring in biochemistry before you start conjecturing.

you set yourself up for some flaming. particularly because your answers didn't do much more than conjecture and I didn't interpret your answers as coming from someone with first hand experience or extensive knowledge in the biological sciences. sorry, undergrad just doesn't cut it, and you'll realize this if you pursue a higher degree.
Also, when you say something like this:

I suppose I'll have to bear it.

and admit you are a mere junior in college, I sense a high arrogance/ knowledge ratio, which probably means arguing will be impossible.

the simple facts are these:

1) everyone has the right to conjecture regardless of their knowledge. And you aren't high enough on the totem pole to tell others below you to shut up. I'm much higher on the pole than you and I think everyones answers count.

2) your assessment that there are only a FEW areas of the creation of life that are not yet understood reeks of ignorance. How do you come to this?

3) you get on this discussion of molecular handedness and don't make any attempt to tie it in to the question at hand: Can a single cell organism be synthesized?

4) using the term 'exponential' to describe costs is ridiculous. also, to say that costs and interests are prohibitive towards the appropriate experimental research required to undertake such a task is wrong. the reason that funding in this area is weak is because NOONE has come up with a good plan on how to do it. That is, there is NO faith that it can be done. and these judgements are made by scientists that know what they are doing.

anyways, keep the cussing out, I'm still interested in hearing your views.

My discussion of molecular handedness was to prop up the fact that inordinate amounts of work would go into purification and synthesization for the molecules in order to make the single celled organism.

Also, when I say the costs are exponential, I am not implying at at 100% the cost is infinite. I would hope that neither you or anyone else would think that way. Suffice it to say that the purer your compounds become (after a certain breaking point), the price jump might as well be exponential.

Also, I would love to be a "PhD with a lifetime of laboratory experience in biochem", but unfortunately I am a silly undergraduate student who has been working in a biochem NMR lab for 2 years. When I say there is a lot of conjecturing going on, I am seeing a lot of people who were opining after watching the Discovery Channel (explore your world).

But let me clear up my stances:
1) Currently it is not possible to create single celled organism - but it is not because we are years and years away from the feat, but rather the scientific community has not focused on this particular feat. Also, creation of a single celled organism from scratch is prohibitively expensive, which is why scientists engineer new virus/bacteria by capitalizing on the functions of existing bacteria/virus and modifying them. If they did NOT understand how these organisms worked, they would be unable to modify them to the extent they are able to do today (and they do some pretty crazy stuff).
So what I am saying is they can, and they could, but it would be a waste of time/money.


2) I have no clue nor do I have an opinion about recreating the origin of life. That is something I did not intend to argue about since the beginning.


And one last thing, gururu - I'll "cuss" when I want. I didn't call you a piece of sh*t, or use the f-word or anything. Bullshit means I think you're quack, and forgive me if you're too quaint to understand my intent. I wasn't trying to be offensive - I honestly felt you were doing nothing but opining. If you do have a greater depth of knowledge and understanding than I do, I'd like to hear your reasoning - otherwise, I will not sit here and accept that you "are higher on the totem pole".

 

[TuxDave]

Originally posted by: Taejin
I'm a junior in college, majoring in biochemistry and biochemical engineering. I study hard and I do well in my classes - I think I do know what I am talking about, unless my professors have been lying to me all this time.

Silly undergrad. Thinking that you're so smart. 😉 It boils down to this:

non-majors < undergraduate majors < industry folk = graduate students < graduate students w/ industry experience

😀 Don't mind me. As a graduate student, I find it amusing to poke fun of undergrads.

 

[Machupo]

so... what precisely is require to create a "rudimentary single-celled organism"?

1. lipid/protinaceous bilayer membrane
2. information carrying molecule (included)

there ya go...

well, i guess if you wanted to stick to the definition of Life?, you'd need a bit of cytoskeletal structure and motility organelles (or microtubule production facility) to allow for fission...

the part that makes this relatively easy is the fact that once you've got the membrane layer established, it is much easier to regulate the environment inside the cell. This allows you to be much more imprecise with your protein construction, in terms of your pseudo-mRNA and ribosomes, etc... after all, if the environment is static, the only part of the protein that matters is the contact map 😉

i've been working on quite a few ideas with SWCNT's and their applications in intracellular movement structures... microtubules are pretty easy to make though, and CNT's require a surprising amount of binding energy if you go at it along the accretion method... so you'd need much larger proteins to crack and roll graphene sheets.

there are definitely some neat ideas floating around in this idea, but i'm no Artifex myself (hopefully someday i'll figure it out and don the hat 😛)

-Nick

 

[CycloWizard]

Originally posted by: jhu
want a bigger philosophical headache? do the entire project digitally using a massive supercomputer. now, given that those digital cells do the same things a real cell does but in a virtual world, do those digital cells constitute life?

I'm running enough numerical simulations right now, thanks. The real headache is trying to match them with analytical solutions. :x

It could possibly tell us how to go about it, but it wouldn't tell us the answer to the question: would it be alive?