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    Jack Szostak And The Origin Of Life
    By Steve Davis | February 19th 2012 02:18 AM | 28 comments | Print | E-mail | Track Comments
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    Nobel Prize winner Jack Szostak recently wrote an opinion piece titled "Attempts to Define Life Do Not Help to Understand the Origin of Life" which was published in the Journal of Biomolecular Structure and Dynamics. (open access, so you can read it free of charge)
     
    The view he expressed was given respectful coverage by Carl Zimmer in his widely publicised article "Can Science Define Life in Three Words", the only blemish from the usually perceptive Zimmer in an otherwise interesting and balanced article.

    Not only is Szostak’s view wrong, but he compounded the error with the opening sentence;
    “Attempts to define life are irrelevant to scientific efforts to understand the origin of life.”  So, not just unhelpful, but irrelevant as well!  

    Let’s see. Let’s put reputation to one side for a moment and put him to the test.

    His article is quite short, so we can examine it in detail.  First, the title; '"Attempts to Define Life Do Not Help to Understand the Origin of Life." That view is not logical. How can we understand the origin of something that is undefined? In fairness to Szostak, we do recognise what life is, by its principal features of growth, metabolism, reproduction and homeostasis, but he has completely overlooked the rather obvious fact that any conclusions that are reached about the origins of life (that being his particular project, his job, his profession) will look extremely questionable, almost laughable, if those conclusions fail to explain the point at which life began. So a definition of life is not only helpful, but relevant as well.  

    He continued; “Simply put, the study of the ‘origin of life’ is an effort to understand the transition from chemistry to biology. This fundamental transition was the result of a lengthy pathway consisting of many stages, each of which is the subject of numerous scientific questions. Simple chemistry in diverse environments on the early earth led to the emergence of ever more complex chemistry and ultimately to the synthesis of the critical biological building blocks. At some point, the assembly of these materials into primitive cells enabled the emergence of Darwinian evolutionary behavior, followed by the gradual evolution of more complex life forms leading to modern life.

    Somewhere in this grand process, this series of transitions from the clearly physical and chemical to the clearly biological, it is tempting to draw a line that divides the non-living from the living. But the location of any such dividing line is arbitrary, and there is no agreement on where it should be drawn. An inordinate amount of effort has been spent over the decades in futile attempts to define ‘life’ – often and indeed usually biased by the research focus of the person doing the defining.


    As a result, people who study different aspects of physics, chemistry and biology will draw the line between life and non-life at different positions. Some will say there is no life until a well defined set of metabolic reactions are in place. Others will focus on spatial compartmentalization, on the various requirements for Darwinian evolution, or on the specific molecules of inheritance. None of this matters, however, in terms of the fundamental scientific questions concerning the transitions leading from chemistry to biology – the true unknowns and subject of origin-of-life studies.”

    “None of this matters in terms of the fundamental scientific questions...” What could be more fundamental to a biologist than defining life? And as for “the true unknowns...” that’s just snobbery.

    Szostak should immediately ditch all his current work and focus on the question of life, because what he has articulated is a disgrace to biology. The problems he outlined illustrate just why biologists cannot agree as to what life is. The competing views that he described have one thing in common; they are all focused on the functions and physical features of entities that are living, not on the underlying essence of the functions and features.

    He continued; “Beyond the arbitrary nature of efforts to define the boundary between non-life and life, this effort is illusory for a deeper reason. As one focuses experimentally on any of the ‘defining’ properties of ‘life’, the sharp boundary seems to blur, splitting into finer and finer sub-divisions. As an example, let us look at the emergence of Darwinian evolution, which is often cited as a key aspect of the definition of life (with good reason, as Darwinian evolution is indeed the unifying characteristic of all of biology).”

    Now he’s indulging his own bias. The unifying feature of biology is not evolution, it is life. (Generalisation can be useful, but not in this instance.) However, Darwinian evolution is the best he can come up with to describe life, which is possibly why he is not keen on discussing a definition, the deficiencies of his position being rather obvious.
     
    But that does not prevent him using it to hijack the topic as he continued; “Certainly once cells with genetically encoded advantageous functions existed, classically defined Darwinian evolution had begun, and most people would define such cells as alive. But what about the previous steps? Such cells would likely have been preceded by protocells, with replicating genetic information, but lacking coded functions that provided a cellular advantage. At this stage, replication with heritable variation would have existed, and whatever process drove replication would most likely have had biases that led to changes in the genetic structure of the population over time.

    Would that minimalist form of evolution qualify such protocells as being alive? Going back even further, consider genetic molecules replicating in solution or on particulate surfaces – again, biases in replication would lead to selection for sequences that are better templates, i.e., easier to replicate. Even the assembly of the first genetic polymers would have had biases, leading to non-random population structures. Darwinian evolution itself emerged in a series of stages, step-by-step, gradually leading to the almost infinite potential for organismal variation seen in modern biology. And yet, to define a single point along the progression as the point at which Darwinian evolution first emerged would be difficult. More importantly, such a definition would not further our understanding of the transitions involved or the nature of the physical and chemical forces driving those transitions.”


    Basically, what he has said there is that it’s just too difficult.

    But, by presenting this as THE argument, he’s also being tricky. By switching from discussing the boundary between non-life and life, to a discussion about the point that evolution began, he has muddied the waters, because they are not the same questions as he would like us to assume, they are very different. The point at which Darwinian evolution first emerged is not the point at which life began. That is so wrong. You first have to have life, then you have to have variation, then natural selection can take effect, then evolution can begin. He is two or three steps behind the game.

    He concluded with; “What is important in the origin of life field is understanding the transitions that led from chemistry to biology. So far, I have not seen that efforts to define life have contributed at all to that understanding.”

    Let’s help him out. The transition from chemistry to biology must have been a relatively simple process, because you cannot have stages of life. Either you have life or you do not. But Szostak cannot see that simplicity.

    You’ll note from his article that complexity is something of a mental hurdle, a fixation that intrudes on his thinking to such an extent that he can’t see the forest for the trees. (And he’s not alone in this. This inability to forget the complexity of modern life forms is a major stumbling block in getting people to think logically about life. Life forms might be complex, but life is not.) But because life forms CAN be complex, Szostak has made the mistake of thinking that life must be complex.

    This intrusion by complexity into Szostak’s thinking can be seen in his regular references to “lengthy pathways” “many stages” “ever more complex chemistry” “grand process” “series of transitions” “series of stages” “single point along the progression...” Those transitions and stages that he refers to are clearly transitions to more complex life forms, as he would concede.
    So he has made the same error as Edward Trifonov, who defined life as “reproduction with variation”.
     
      While they both see life correctly as a process, they both make the mistake of focusing on the outcome of the process, instead of the driver of the process.  The driver of the process is molecular cooperation, Szostak’s field of expertise. The field in which he’s worked for twenty years, so the irony of this is beyond belief.

      Cooperation sparked the first life forms, so cooperation IS life. The transition from chemistry to biology was brought about in one step by cooperation. Chemistry – spark – biology.
    That's how simple it is.

    It’s all about forests and trees.
     
    NOTES

    The argument above shows that the definition or theory of life, and the origin of life are not only linked; they are complementary – each assists an understanding of the other, which, when you think about it, is how it should be.

    I must thank the Journal of Biomolecular Structure and Dynamics for making articles available online. 

    Comments

    Bonny Bonobo alias Brat
    Very thought provoking article. Steve. You say that :- "The problems he outlined illustrate just why biologists cannot agree as to what life is. The competing views that he described have one thing in common; they are all focused on the functions and physical features of entities that are living, not on the underlying essence of the functions and features." You also say "Its all about forest and trees" but isn't it really all about forest, trees and lichen? This debate about what life is reminds me of the ongoing psychological debate about what intelligence is? Sometimes arguing about definitions really does get us nowhere, even when there is a general consensus as to what both intelligence and life really mean, there is no consensus on their definitions and in my opinion there probably never will be. However, we still need to study the origins of life and intelligence even if we can't irrefutably define them don't we?
    My latest forum article 'Australian Researchers Discover Potential Blue Green Algae Cause & Treatment of Motor Neuron Disease (MND)&(ALS)' Parkinsons's and Alzheimer's can be found at http://www.science20.com/forums/medicine
    Steve Davis
    Thanks for the comment Helen.
    I see your point with the debate about intelligence, but if you accept the theory of life as cooperation, you must admit that perhaps intelligence is also a case of seeing complexity where none exists.
    I'm not commenting either way, by the way.
    You said that life can't be irrefutably defined, so I guess you now have to refute my view!  :)
    Bonny Bonobo alias Brat
    "you must admit that perhaps intelligence is also a case of seeing complexity where none exists." Actually Steve, I think that intelligence is always a very complex subject which is why I think any seriously useful artificial intelligence (AI) is highly unlikely to be created by man any more than man is likely to be able to create any real life form from chemicals. But I agree with you that to some extent defining life is important for understanding the origins of life, I just doubt if you will ever be able to get a consensus on that definition. Likewise defining intelligence is important for understanding the origins of intelligence but again a consensus is unlikely and so is an AI without life probably. I guess then that I am also therefore agreeing with Szostac when he says "to define a single point along the progression as the point at which Darwinian evolution first emerged would be difficult. More importantly, such a definition would not further our understanding of the transitions involved or the nature of the physical and chemical forces driving those transitions. What is important in the origin of life field is understanding the transitions that led from chemistry to biology. So far, I have not seen that efforts to define life have contributed at all to that understanding."
    My latest forum article 'Australian Researchers Discover Potential Blue Green Algae Cause & Treatment of Motor Neuron Disease (MND)&(ALS)' Parkinsons's and Alzheimer's can be found at http://www.science20.com/forums/medicine
    Steve Davis
    "I just doubt if you will ever be able to get a consensus on that definition." Well, it's like this, Helen. People who read the article have three options. They can agree with it, or they can refute it, or they can walk away and pretend they have not read it. "I guess then that I am also therefore agreeing with Szostac when he says "to define a single point along the progression as the point at which Darwinian evolution first emerged would be difficult..." But Helen, the point at which Darwinian evolution emerged is not relevant to a discussion about the emergence of life, as I explained in the article.
    Bonny Bonobo alias Brat
    I agree that Szostak muddies the water when he talks about these Darwinian aspects of life but i agree with him when he says :- "An inordinate amount of effort has been spent over the decades in futile attempts to define ‘life’ – often and indeed usually biased by the research focus of the person doing the defining. As a result, people who study different aspects of physics, chemistry and biology will draw the line between life and non-life at different positions." Surely you are now giving an example of this by saying :- "The driver of the process is molecular cooperation, Szostak’s field of expertise. The field in which he’s worked for twenty years, so the irony of this is beyond belief." ... "Cooperation sparked the first life forms, so cooperation IS life. The transition from chemistry to biology was brought about in one step by cooperation. Chemistry – spark – biology. That's how simple it is." Steve are you saying that molecular cooperation is the definition of life that everyone should now agree? Couldn't there also even be some molecules that hypothetically lived and then died just for a second without cooperating? Couldn't they then be the basic units of life that preceded cooperating molecules? Where do you draw the line? I tend to agree with you though, cooperating molecules make the most sense to me as a definition of life but good luck at getting everyone to agree with that definition.
    My latest forum article 'Australian Researchers Discover Potential Blue Green Algae Cause & Treatment of Motor Neuron Disease (MND)&(ALS)' Parkinsons's and Alzheimer's can be found at http://www.science20.com/forums/medicine
    Steve Davis
    "Couldn't there also even be some molecules that hypothetically lived and then died just for a second without cooperating?" No. "Couldn't they then be the basic units of life that preceded cooperating molecules?" On what basis can they be considered to be alive? "Where do you draw the line?" At molecular cooperation. Keep in mind that we are talking here of the origin of life, but the cooperation explanation holds true for all levels of life. "I tend to agree with you though, cooperating molecules make the most sense to me as a definition of life but good luck at getting everyone to agree with that definition." Thanks for that Helen. As for getting everyone to agree, I think the big hurdle there is that most people, like Jack Szostak, assume that life is complex, so they have trouble even considering an explanation so simple as cooperation.
    Gerhard Adam
    No matter how you view the problem, it is clear that at some point there were oscillating chemical reactions that needed to be maintained.  I realize the word "needed" is going to raise all kinds of hackles, but the point is that what distinguishes life from any other chemical reaction is the degree of control the living organism is capable of exercising over these reactions.

    Therefore at some point, chemistry that was capable of maintaining control over its resources (i.e. self-contained) and was able to control the molecules entering the reaction as well as the products of that reaction and therefore, could likely be considered the first forms of life.

    Now some people will object because it assigns a kind of "intent" to the process that they don't believe can exist, but that begs the question.  In other words, any chemical reaction that could not be controlled or was dependent on the random arrival of molecules was doomed to fade out.  It was only those unique configurations that could maintain such reactions indefinitely that had any chance of maintaining a consistent existence and ultimately replicating that process.
    Mundus vult decipi
    Steve Davis
    These are all very good points that you raise Gerhard. "..what distinguishes life from any other chemical reaction is..." But life is not a chemical reaction, it is the process driving the chemistry. "Therefore at some point, chemistry that was capable of maintaining control over its resources (i.e. self-contained) and was able to control the molecules entering the reaction as well as the products of that reaction and therefore, could likely be considered the first forms of life." I agree. "In other words, any chemical reaction that could not be controlled or was dependent on the random arrival of molecules was doomed to fade out." Exactly. Simple natural selection. "It was only those unique configurations that could maintain such reactions indefinitely that had any chance of maintaining a consistent existence and ultimately replicating that process." In other words, the best cooperators survived. The underlying factor in all of this Gerhard, the driver of these processes and outcomes, is cooperation.
    Gerhard Adam
    But life is not a chemical reaction, it is the process driving the chemistry.
    That's too subtle a distinction for me, since it is clear that chemistry had to give rise to "something" before there could be any processes for anything.  I don't think there's any question that natural selection drove organisms in directions where such control became essential and could justifiably be said to drive the reactions.  After all, it would be difficult to argue that respiration drives the organism, since it is the genetics of the organism that create the respiratory system.

    So, perhaps the transition from reaction to process is that crucial "cut-over" point to what we would call "life".
    Mundus vult decipi
    Steve Davis
    "That's too subtle a distinction for me,.." But it's not subtle Gerhard. It's simple, but not subtle. "...it is clear that chemistry had to give rise to "something" before there could be any processes for anything." Not at all! You can have chemical processes without life. A reaction is a process. The "crucial cut-over point" you refer to is the point at which entities cooperate.
    Gerhard Adam
    I suppose that one could describe the whole concept of a "process" as being a series of cooperative steps.  In other words, the only way to ensure that a process is self-perpetuating (or continuous), is if every contributing component of it "does their part".  So, in that respect one could define cooperation without "intent" or "goal" beyond repetitively doing what each component does which keeps the entire mechanism going.

    Mundus vult decipi
    Steve Davis
    Gerhard, I could hug you!
    "Cooperation sparked the first life forms, so cooperation IS life. The transition from chemistry to biology was brought about in one step by cooperation. Chemistry – spark – biology.
    That's how simple it is."

    How do you define "cooperation"?
    To me cooperation signifies a form of goal oriented behaviour, of which molecules are incapable of...
    Do you mean some kind of resonace perhaps?

    Steve Davis
    Mattias, thanks for your interest.
    The term "molecular cooperation" is commonly used in molecular biology.
    I see cooperation as "functioning for mutual benefit", so if the functions of molecules result in a benefit, they are cooperating, there does not have to be a goal.
    Gerhard Adam
    Perhaps "goal" is too strong an anthropomorphic concept.  It might be better to consider it like the ground state of electrons.  It's a kind of "path of least resistance" so that the optimal/minimal amount of energy is committed for something to occur. 

    In other words, to consider Hydrogen combining with Oxygen to form water is an intentional concept, unless we consider that if this chemical combination is the easiest to achieve with the least amount of energy, then the "cooperation" of these atoms has succeeded.  The formation of water is simply the by-product of seeking the optimal reaction.
    Mundus vult decipi
    Steve Davis
    "The formation of water is simply the by-product of seeking the optimal reaction." Exactly Gerhard. And that principle applies as we go up the chain. The next step from chemistry to biology as Jack Szostak likes to put it, would also have been a simple step if conditions were favourable.
    Bonny Bonobo alias Brat
    So does that mean that quantum entangled molecules as big as 'buckyballs' (whatever they are?) and diamonds are also alive? Wiki describes how "Quantum entanglement occurs when particles such as photons, electrons, molecules as large as "buckyballs",and even small diamonds interact physically and then become separated; the type of interaction is such that each resulting member of a pair is properly described by the same quantum mechanical description (state), which is indefinite in terms of important factors such as position, momentum, spin, polarization, etc." "According to the Copenhagen interpretation of quantum mechanics, their shared state is indefinite until measured.[ Quantum entanglement is a form of quantum superposition. When a measurement is made and it causes one member of such a pair to take on a definite value (e.g., clockwise spin), the other member of this entangled pair will at any subsequent time be found to have taken the appropriately correlated value (e.g., counterclockwise spin). Thus, there is a correlation between the results of measurements performed on entangled pairs, and this correlation is observed even though the entangled pair may have been separated by arbitrarily large distances." Surely this is also a form of molecular cooperation and therefore life?
    My latest forum article 'Australian Researchers Discover Potential Blue Green Algae Cause & Treatment of Motor Neuron Disease (MND)&(ALS)' Parkinsons's and Alzheimer's can be found at http://www.science20.com/forums/medicine
    Gerhard Adam
    No.
    Mundus vult decipi
    Bonny Bonobo alias Brat
    No? Why not? There are now plenty of examples of molecules and now even macroscopic diamonds at room temperature 'cooperating' via quantum entanglement. According to Steve's definition of life being 'cooperating molecules' then surely these molecules and diamonds are temporarily alive while they are entangled, until we measure them and inadvertently kill them?

    In the case of the quantum entangled diamonds see this Scientific American article at http://www.scientificamerican.com/article.cfm?id=room-temperature-entang... "To entangle relatively large objects, Walmsley and his colleagues harnessed a collective property of diamonds: the vibrational state of their crystal lattices. By targeting a diamond with an optical pulse, the researchers can induce a vibration in the diamond, creating an excitation called a phonon—a quantum of vibrational energy. Researchers can tell when a diamond contains a phonon by checking the light of the pulse as it exits. Because the pulse has deposited a tiny bit of its energy in the crystal, one of the outbound photons is of lower energy, and hence longer wavelength, than the photons of the incoming pulse."

    "Walmsley and his colleagues set up an experiment that would attempt to entangle two different diamonds using phonons. They used two squares of synthetically produced diamond, each three millimeters across. A laser pulse, bisected by a beam splitter, passes through the diamonds; any photons that scatter off of the diamond to generate a phonon are funneled into a photon detector. One such photon reaching the detector signals the presence of a phonon in the diamonds."

    "Once again, there is no way of knowing which diamond produced the photon, because the paths leading from each diamond to the detectors are merged, so there is no way of knowing where the phonon was. But the researchers found that each of the photon paths leading from the diamonds to the detectors had an interfering effect on the other—adjusting how the two paths were joined affected the photon counts in the detectors. In essence, a single photon reaching the detectors carried information about both paths. So it cannot be said to have traveled down one path from one diamond: the photon, as with the vibrational phonon that produced it, came from both diamonds."

    "After running the experiment over and over again to gather statistically significant results, the researchers concluded with confidence that entanglement had indeed been achieved." In other words the two separate diamonds' and their molecules were cooperating and they were even maybe temporarily alive if we accept Steve's definition of life which is cooperating molecules?
    My latest forum article 'Australian Researchers Discover Potential Blue Green Algae Cause & Treatment of Motor Neuron Disease (MND)&(ALS)' Parkinsons's and Alzheimer's can be found at http://www.science20.com/forums/medicine
    Steve Davis
    Helen, there's more to life forms than a definition of life.
    Bonny Bonobo alias Brat
    Yes Steve and there are lots of definitions of life that people don't agree upon. I'm just demonstrating how the 'cooperating molecules' definition of life could almost be used to include quantum entangled molecules and even these entangled diamonds. After all entanglement is very 'spooky' and difficult to explain, maybe the molecules that we are composed of are also entangled? Maybe life did follow on from entangled molecules, is that really such a ridiculous concept?
    My latest forum article 'Australian Researchers Discover Potential Blue Green Algae Cause & Treatment of Motor Neuron Disease (MND)&(ALS)' Parkinsons's and Alzheimer's can be found at http://www.science20.com/forums/medicine
    Steve Davis
    Helen, the quantum arena is the foundation of the macro world, so speculation as to the process that led to life is not ridiculous. But life forms have recognisable features, metabolism probably being the most important, and it's doubtful that metabolism can be found at the quantum level, (though nothing should be ruled out,) so it's also doubtful that life would be found there. However, forerunners to the process might be.
    Gerhard Adam
    The answer is still no.
    Mundus vult decipi
    The issues discussed herein are answered in detail in my book Encounter of science with Philosophy - A synthetic view. Chapter -28 defines life and enumerates and describes various aspects of phenomenon of life (>55 in number).According to the views expressed in the book viruses are to be regarded as living beings and nothing else.
    Chapter - 29 deals with origin of life , suggests mechanism of origin of life, rules out need for prebiotic soup and existence of LUCA. Predicts that life could have started as a small circular DNA molecule just 250 nucleotide base long. Suggested mechanism of origin of life can be viewed as corollary of definition of life given in my book.
    Lastly I think Jack Szostak is completely wrong in his views.
    To know more about my views visit www.sciencengod.com/clipboard
    However please understand that you shall be able to fully appreciate my views and make fair comments only after you have read the book.

    Steve Davis
    Thanks for your interest, but the primary consideration here is not the selling of books.
    Please feel free to summarise your views in an article.
    The issue is not selling of books. The issue is that subject matter contained in 69 pages (printed version) of my book can not be justifiably dealt with in a blog . But only to partially satisfy you I write the following:-

    "Life is defined as a functional system consisting of an intelligent molecular ensemble capable of keeping its being and purposeful response to environment"

    Please let me know your objections to the above said.

    Consciousness materially expressed as natural computing / natural intelligence / molecular computing / DNA Computing / RNA Computing / Peptide Computing etc., is the driver of the phenomenon called Origin of Life and even Origin of Universe.

    In fact consciousness had to precede creation of even the first photon to counteract dissipation of its energy under the effect of SECOND LAW OF THERMODYNAMICS which has been renamed by me as Law of energy flow.

    Again you are requested to publish your objections to the above said.

    Steve Davis
    "Life is defined as a functional system consisting of an intelligent molecular ensemble capable of keeping its being and purposeful response to environment"
    What you have given here is a very good description of a life form, not of life.
    You've fallen into the same trap we all fall into, the language trap, as I explained here.
    Life is not an "ensemble", it is not physical, it is a process.
    To define life we have to look at the essence of the system.

    Thanks for your thoughts on consciousness, but these are more in the realm of quantum physics, an area into which I'm not prepared to venture too far.
    May God help you