All posts tagged the Human Genome

What Is Life? How Chemistry Becomes Biology by Addy Pross (2012)

I will attempt to show that the chasm separating biology and chemistry is bridgeable, that Darwinian theory can be integrated into a more general chemical theory of matter, and that biology is just chemistry, or to be more precise, a sub-branch of chemistry – replicative chemistry. (p.122)

Repetitive and prolix

This book is 190 pages long. It is much harder to read than it need be because Pross is a bad writer with very bad habits, namely 1. irritating repetition and 2. harking back and forward. The initial point which he repeats again and again in the first 120 pages is that nobody knows the secret of the origins of life and all previous attempts to solve it have been dead ends.

So, what can we conclude regarding the emergence of life on our planet? The short answer: almost nothing. (p.109)

We don’t know how to go about making life because we don’t really know what life is, and we don’t know what life is, because we don’t understand the principles that led to its emergence. (p.111)

The efforts to uncover probiotic-type chemistry, while of considerable interest in their own right, were never likely to lead us to the ultimate goal – understanding how life on earth emerged. (p.99)

Well, at the time of writing, the so-called Holy Grail (the Human Genome sequence) and the language of life that it was supposed to have taught us have not delivered the promised goods. (p.114)

But the systems biology approach has not proved a nirvana… (p.116)

Non-equilibrium thermodynamics has not proved to be the hoped-for breakthrough in seeking greater understanding of biological complexity. (p.119)

A physically based theory of life continues to elude us. (p.119)

While Conway’s Life game has opened up interesting insights into complex systems in general, direct insights into the nature of living systems do not appear to have been forthcoming. (p.120)

The book is so repetitive I though the author and his editor must have Alzheimer’s Disease. On page viii we are told that the physicist Erwin Schrödinger wrote a pithy little book titled What Is Life? which concluded that present-day physics and chemistry can’t explain the phenomenon of life. Then, on page xii, we’re told that the physicist Erwin Schrödinger’ found the issue highly troublesome’. Then on page 3 that the issue ‘certainly troubled the great physicists of the century, amongst them Bohr, Schrödinger and Wigner’. Then on page 36, we learn that:

Erwin Schrödinger, the father of quantum mechanics, whose provocative little book What Is Life? we mentioned earlier, was particularly puzzled by life’s strange thermodynamic behaviour.

When it comes to Darwin we are told on page 8 that:

Darwin himself explicitly avoided the origin of life question, recognising that within the existing state of knowledge the question was premature.

and then, in case we have senile dementia or the memory of a goldfish, on page 35 he tells us that:

Darwin deliberately side-stepped the challenge, recognising that it could not be adequately addressed within the existing state of knowledge.

As to the harking back and forth, Pross is one of those writers who is continually telling you he’s going to tell you something, and then continually reminding you that he told you something back in chapter 2 or chapter 4 – but nowhere in the reading process do you actually get clearly stated the damn thing he claims to be telling.

As we mentioned in chapter 4…

As noted above…

I will say more on this point subsequently…

We will consider a possible resolution of this sticky problem in chapter 7…

As discussed in chapter 5… as we will shortly see… As we have already pointed out… As we have discussed in some detail in chapter 5…  described in detail in chapter 4…

In this chapter I will describe… In this chapter I will attempt…

I will defer this aspect of the discussion until chapter 8…

Jam yesterday, jam tomorrow, but never jam today.

Shallow philosophy

It is a philosophy book written by a chemist. As such it comes over as extremely shallow and amateurish. Pross namechecks Wittgenstein, and (pointlessly) tells us that ‘tractatus’ is Latin for ‘treatise’ (p.48) – but fails to understand or engage with Wittgenstein’s thought.

My heart sank when I came to chapter 3, titled Understanding ‘understanding’ which boils down to a superficial consideration of the difference between a ‘reductionist’ and a ‘holistic’ approach to science, the general idea that science is based on reductionism i.e. reducing systems to their smallest parts and understanding their functioning before slowly building up in scale, whereas ‘holistic’ approach tries to look at the entire system in the round. Pross gives a brief superficial overview of the two approaches before concluding that neither one gets us any closer to an answer.

Instead of interesting examples from chemistry, shallow examples from ‘philosophy’

Even more irritating than the repetition is the nature of the examples. I thought this would be a book about chemistry but it isn’t. Pross thinks he is writing a philosophical examination of the meaning of life, and so the book is stuffed with the kind of fake everyday examples which philosophers use and which are a) deeply patronising b) deeply uninformative.

Thus on page x of the introduction Pross says imagine you’re walking through a field and you come across a refrigerator. He then gives two pages explaining how a refrigerator works and saying that you, coming across a fully functional refrigerator in the middle of a field, is about as probable as the purposeful and complex forms of life can have come about by accident.

Then he writes, Imagine that you get into a motor car. We only dare drive around among ‘an endless stream of vehicular metal’ on the assumption that the other drivers have purpose and intention and will stick to the laws of the highway code.

On page 20 he introduces us to the idea of a ‘clock’ and explains how a clock is an intricate mechanism made of numerous beautifully engineered parts but it will eventually break down. But a living organism on the other hand, can repair itself.

Then he says imagine you’re walking down the street and you bump into an old friend named Bill. He looks like Bill, he talks like Bill and yet – did you know that virtually every cell in Bill’s body has renewed itself since last time you saw him, because life forms have this wonderful ability to repair and renew themselves!

Later, he explains how a Boeing 747 didn’t come into existence spontaneously, but was developed from earlier plane designs, all ultimately stemming from the Wright brothers’ first lighter than air flying machine.

You see how all these examples are a) trite b) patronising c) don’t tell you anything at all about the chemistry of life.

He tells us that if you drop a rock out the window, it falls to the ground. And yet a bird can hover in the air merely by flapping its wings! For some reason it is able to resist the Second law of Thermodynamics! How? Why? Nobody knows!

Deliberately superficial

And when he does get around to explaining anything, Pross himself admits that he is doing it in a trivial, hurried, quick, sketchy way and leaving out most of the details.

I will spare the reader a detailed discussion…

These ideas were discussed with some enthusiasm some 20-30 years ago and without going into further detail…

If that sounds too mathematical, let’s explain the difference by recounting the classical legend of the Chinese emperor who was saved in battle by a peasant farmer. (p.64)

Only in the latter pages – only when he gets to propound his own theory from about page 130 – do you realise that he is not so much making a logical point as trying to get you to see the problem from an entirely new perspective. A little like seeing the world from the Marxist or the Freudian point of view, Pross believes himself to be in possession of an utterly new way of thinking which realigns all previous study and research and thinking on the subject. It is so far-ranging and wide-sweeping that it cannot be told consecutively.

And it’s this which explains the irritating sense of repetition and circling and his constant harking forward to things he’s going to tell you, and then harking back to things he claims to have explained a few chapters earlier. The first 130 pages are like being lost in a maze.

The problem of the origin of life

People have been wondering about the special quality of live things as opposed to dead things for as long as there have been people. Darwin discovered the basis of all modern thinking about life forms, which is the theory of evolution by natural selection. But he shied away from speculating on how life first came about.

Pross – in a typically roundabout manner – lists the ‘problems’ facing anyone trying to answer the question, What is life and how did it begin?

  • life breaks the second law of thermodynamics i.e. appears to create order out of chaos, as opposed to the Law which says everything tends in the opposite direction i.e. tends towards entropy
  • life can be partly defined by its sends of purpose: quite clearly inanimate objects do not have this
  • life is complex
  • life is organised

Put another way, why is biology so different from chemistry? How are the inert reactions of chemistry different from the purposive reactions of life? He sums this up in a diagram which appears several times:

He divides the move from non-life into complex life into two phases. The chemical phase covers the move from non-life to simple life, the biological phase covers the move from simple life to complex life. Now, we know that the biological phase is covered by the iron rules of Darwinian evolution – but what triggered, and how can we account for, the move from non-life to simple life? Hence a big ?

Pross’s solution

Then, on page 127, Pross finally introduces his Big Idea and spends the final fifty or so pages of the book showing how his theory addresses all the problem in existing ‘origin of life’ literature.

His idea begins with the established knowledge that all chemical reactions seek out the most ‘stable’ format.

He introduces us to the notion that chemists actually have several working definitions of ‘stability’, and then introduces us to a new one: the notion of dynamic kinetic stability, or DKS.

He describes experiments by Sol Spiegelman in the 1980s into RNA. This showed how the RNA molecule replicated itself outside of a living cell. That was the most important conclusion of the experiment. But they also found that the RNA molecules replicated but also span off mutations, generally small strands of of RNA, some of which metabolised the nutrients far quicker than earlier varieties. These grew at an exponential rate to swiftly fill the petri dishes and push the longer, ‘correct’ RNA to extinction.

For Pross what Spiegelman’s experiments showed was that inorganic dead chemicals can a) replicate b) replicate at exponential speed until they have established a situation of dynamic kinetic stability. He then goes on to equate his concept of dynamic kinetic stability with the Darwinian one of ‘fitness’. Famously, it is the ‘fit’ which triumph in the never-ending battle for existence. Well, Pross says this concept can be rethought of as, the population which achieves greatest dynamic kinetic stability – which replicates fast enough and widely enough – will survive, will be the fittest.

fitness = dynamic kinetic stability (p.141)

Thus Darwin’s ideas about the eternal struggle for existence and the survival of the fittest can be extended into non-organic chemistry, but in a particular and special way:

Just as in the ‘regular’ chemical world the drive of all physical and chemical systems is toward the most stable state, in the replicative world the drive is also toward the most stable state, but of the kind of stability applicable within that replicative world, DKS. (p.155)

Another way of looking at all this is via the Second Law. The Second Law of Thermodynamics has universally been interpreted as militating against life. Life is an affront to the Law, which says that all energy dissipates and seeks out the state of maximum diffusion. Entropy always triumphs. But not in life. How? Why?

But Pross says that, if molecules like his are capable of mutating and evolving – as the Sol Spiegelman experiments suggest – then they only appear to contradict the Second Law. In actual fact they are functioning in what Pross now declares is an entirely different realm of chemistry (and physics). The RNA replicating molecules are functioning in the realm of replicative chemistry. They are still inorganic, ‘dead’ molecules – but they replicate quickly, mutate to find the most efficient variants, and reproduce quickly towards a state of dynamic kinetic stability.

So what he’s trying to do is show how it is possible for long complex molecules which are utterly ‘dead’, nonetheless to behave in a manner which begins to see them displaying qualities more associated with the realm of biology:

  • ‘reproduction’ with errors
  • triumph of the fittest
  • apparent ‘purpose’
  • the ability to become more complex

None of this is caused by any magical ‘life force’ or divine intervention (the two bogeymen of life scientists), but purely as a result of the blind materialistic forces driving them to take most advantage of their environment i.e. use up all its nutrients.

Pross now takes us back to that two-step diagram of how life came about, shown above – Non-Life to Simple Life, Simple Life to Complex Life, labelled the Chemical Phase and the Biological Phase, respectively.

He recaps how the second phase – how simple life evolves greater complexity – can be explained using Darwin’s theory of evolution by natural selection: even the most primitive life forms will replicate until they reach the limits of the available food sources, at which point any mutation leading to even a fractional differentiation in the efficiency of processing food will give the more advanced variants an advantage. The rest is the three billion year history of life on earth.

It is phase one – the step from non-life to life – which Pross has (repeatedly) explained has given many of the cleverest biologists, physicists and chemists of the 20th century sleepless nights, and which – in chapters 3 and 4 – he runs through the various theories or approaches which have failed to deliver an answer to.

Well, Pross’s bombshell solution is simple. There are not two steps – there was only ever one step. The Darwinian mechanism by which the best adapted entity wins out in a given situation applies to inert chemicals as much as to life forms.

Let me now drop the bombshell… The so-called two-stage process is not two-stage at all. It is really just once, continuous process. (p.127) … what is termed natural selection within the biological world is also found to operate in the chemical world… (p.128)

Pross recaps the findings of that Spiegelman experiment, which was that the RNA molecules eventually made errors in their replication, and some of the erroneous molecules were more efficient at using up the nutrition in the test tube. After just a day, Spiegelman found the long RNA molecules – which took a long time to replicate – were being replaced by much shorter molecules which replicated much quicker.

There, in a nutshell, is Pross’s theory in action. Darwinian competition, previously thought to be restricted only to living organisms, can be shown to apply to inorganic molecules as well – because inorganic molecules themselves show replicating, ‘competitive’ behaviour.

For Pross this insight was confirmed in experiments conducted by Gerald Joyce in 2009, who showed that a variety of types of RNA, placed in a nutrient, replicated in such a way as to establish a kind of dynamic equilibrium, where each molecule established a chemical niche and thrived on some of the nutrients, while other RNA varieties evolved to thrive on other types. To summarise:

The processes of abiogenesis and evolution are actually one physicochemical process governed by one single mechanism, rather than two discrete processes governed by two different mechanisms. (p.136)

Or:

The study of simple replicating systems has revealed an extraordinary connection – that Darwinian theory, that quintessential biological principle, can be incorporated into a more general chemical theory of evolution, one that encompasses both living and non-living systems. it is that integration that forms the basis of the theory of life I propose. (p.162)

The remaining 50 or so pages work through the implications of this idea or perspective. For example he redefines the Darwinian notion of ‘fitness’ to be ‘dynamic kinetic stability’. In other words, the biological concept of ‘fitness’ turns out, in his theory, to be merely the biological expression of a ‘more general and fundamental chemical concept’ (p.141).

He works through a number of what are traditionally taken to be life’s attributes and reinterprets in the new terms he’s introduced, in terms of dynamic kinetic stability, replicative chemistry and so on. Thus he addresses life’s complexity, life’s instability, life’s dynamic nature, life’s diversity, life’s homochirality, life’s teleonomic character, the nature of consciousness, and speculating about what alien life would look like before summing up his theory. Again.

A solution to the primary question exists and is breathtakingly simple: life on earth emerged through the enormous kinetic power of the replication reaction acting on unidentified, but simple replicating systems, apparently composed of chain-like oligomeric substances, RNA or RNA-like, capable of mutation and complexification. That process of complexification took place because it resulted in the enhancement of their stability – not their thermodynamic stability, but rather the relevant stability in the world of replicating systems, their DKS. (p.183)

A thought about the second law

Pross has explained that the Second Law of Thermodynamics apparently militates against the spontaneous generation of life, in any form, because life is organised and the second law says everything tends towards chaos. But he comes up with an ingenious solution. If one of these hypothetical early replicating molecules acquired the ability to generate energy from light – it would effectively bypass the second law. It would acquire energy from outside the ‘system’ in which it is supposedly confined and in which entropy prevails.

The existence of an energy-gathering capacity within a replicating entity effectively ‘frees’ that entity from the constraints of the Second Law in much the same way that a car engine ‘free’s a car from gravitational constrains. (p.157)

This insight shed light on an old problem, and on a fragment of the overall issue – but it isn’t enough by itself to justify his theory.

Thoughts

Several times I nearly threw away the book in my frustration before finally arriving at the Eureka moment about page 130. From there onwards it does become a lot better. As you read Pross you have the sense of a whole new perspective opening up on this notorious issue.

However, as with all these theories, you can’t help thinking that if his theory had been at all accepted by the scientific community – then you’d have heard about it by now.

If his theory really does finally solve the Great Mystery of Life which all the greatest minds of humanity have laboured over for millennia… surely it would be a bit better known, or widely accepted by his peers?

The theory relies heavily on results from Sol Spiegelman’s experiments with RNA in the 1980s. Mightn’t Spiegelman himself, or other tens of thousands of other biologists, have noticed its implications in the thirty odd years between the experiments and Pross’s book?

And if Pross has solved the problem of the origin of life, how come so many other, presumably well-informed and highly educated scientists, are still researching the ‘problem’?

(By the way, the Harvard website optimistically declares that:

Thanks to advances in technologies in these areas, answers to some of the compelling questions surrounding the origins of life in the universe were now possibly within reach… Today a larger team of researchers have joined this exciting biochemical ‘journey through the Universe’ to unravel one of humankind’s most compelling mysteries – the origins of life in the Universe.

‘Possibly within reach’, lol. Good times are always just around the corner in the origins-of-life industry.)

So I admit to being interested by pages 130 onwards of his book, gripped by the urgency with which he tells his story, gripped by the vehemence of his presentation, in the same way you’d be gripped by a thriller while you read it. But then you put it down and forget about it, going back to your everyday life. Same here.

It’s hard because it is difficult to keep in mind Pross’s slender chain of argumentation. It rests on the two-stage diagram – on Pross’s own interpretation of the Spiegelman experiments – on his special idea of dynamic kinetic stability – and on the idea of replicative chemistry.

All of these require looking at the problem through is lens, from his perspective – for example agreeing with the idea that the complex problem of the origin of life can be boiled down to that two-stage diagram; this is done so that we can then watch him pull the rabbit out of the hat by saying it needn’t be in two stages after all! So he’s address the problem of the diagram. But it is, after all, just one simplistic diagram.

Same with his redefining Darwin’s notion of ‘fitness’ as being identical to his notion of dynamic kinetic stability. Well, if he says so. but in science you have to get other scientists to agree with you, preferably by offering tangible proof.

These are more like tricks of perspective than a substantial new theory. And this comes back to his rhetorical strategy of repetition, to the harping on the same ideas.

The book argues its case less with evidence (there is, in the end, very little scientific ‘evidence’ for his theory – precisely two experiments, as far as I can see), but more by presenting a raft of ideas in their current accepted form (for 130 boring pages), and then trying to persuade you to see them all anew, through his eyes, from his perspective (in the final 50 pages). As he summarises it (yet again) on page 162:

The emergence of life was initiated by the emergence of a single replicating system, because that seemingly inconsequentual event opened the door to a distinctly different kind of chemistry – replicative chemistry. Entering the world of replicative chemistry reveals the existence of that other kind of stability in nature, the dynamic kinetic stability of things that are good at making more of themselves.Exploring the world of replicative chemistry helps explain why a simple primordial replicating system would have been expected to complexify over time. The reason: to increase its stability – its dynamic kinetic stability (DKS).

Note the phrase’ entering the world of replicative chemistry…’ – It sounds a little like ‘entering the world of Narnia’. It is almost as if he’s describing a religious conversion. All the facts remain the same, but new acolytes now see them in a totally different light.

Life then is just the chemical consequences that derive from the power of exponential growth operating on certain replicating chemical systems. (p.164)

(I am quoting Pross at length because I don’t want to sell his ideas short; I want to convey them as accurately as possible, and in his own words.)

Or, as he puts it again a few pages later (you see how his argument proceeds by, or certainly involves a lot of, repetition):

Life then is just a highly intricate network of chemical reactions that has maintained its autocatalytic capability, and, as already noted, that complex network emerged one step at a time starting from simpler netowrks. And the driving force? As discussed in earlier chapter, it is the drive toward greater DKS, itself based on the kinetic power of replication, which allows replicating chemical systems to develop into ever-increasing complex and stable forms. (p.185)

It’s all reasonably persuasive when you’re reading the last third of his book – but oddly forgettable once you put it down.

Fascinating facts and tasty terminology

Along the way, the reader picks up a number of interesting ideas.

  • Panspermia – the theory that life exists throughout the universe and can be carried on meteors, comets etc, and one of these landed and seeded life on earth
  • every adult human is made up of some ten thousand billion cells; but we harbour in our guts and all over the surface of our bodies ten times as many – one hundred thousand bacteria. In an adult body hundreds of billions of new cells are created daily in order to replace the ones that die on a daily basis
  • in 2017 it was estimated there may be as many as two billion species of bacteria on earth
  • the Principle of Divergence – many different species are generated from a few sources
  • teleonomy – the quality of apparent purposefulness and goal-directedness of structures and functions in living organisms
  • chiral – an adjective meaning a molecule’s mirror image is not superimposable upon the molecule itself: in fact molecules often come in mirror-image formations, known as left and right-handed
  • racemic – a racemic mixture, or racemate, is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule.
  • reductionist – analysing and describing a complex phenomenon in terms of its simple or fundamental constituents
  • holistic – the belief that the parts of something are intimately interconnected and explicable only by reference to the whole
  • Second Law of Thermodynamics – ‘in all energy exchanges, if no energy enters or leaves the system, the potential energy of the state will always be less than that of the initial state.’ This is also commonly referred to as entropy
  • the thermodynamic consideration – chemical reactions will only take place if the reaction products are of lower free energy than the reactants
  • catalyst – a substance that increases the rate of a chemical reaction without itself undergoing any permanent chemical change
  • catalytic – requires an external catalyst to spark a chemical reaction
  • auocatalytic – a reaction which catalyses itself
  • cross-catalysis – two chemicals trigger reactions in each other
  • static stability – water, left to itself, is a stable chemical compound
  • dynamic stability – a river is always a river even though it is continually changing
  • prebiotic earth – earth before life
  • abiogenesis – the process whereby life was derived from non-living chemicals
  • systems chemistry – the chemical reactions of replicating molecules and the networks they create
  • the competitive exclusion principle – complete competitors cannot co-exist, or, Ecological differentiation is th enecessary condition for co-existence

Does anyone care?

Pross thinks the fact that biologists and biochemists can’t account for the difference between complex but inanimate molecules, and the simplest actual forms of life – bacteria – is a Very Important Problem. He thinks that:

Until the deep conceptual chasm that continues to separate living and non-living is bridged, until the two sciences – physics and biology – can merge naturally, the nature of life, and hence man’s place in the universe, will continue to remain gnawingly uncertain. (p.42)

‘Gnawingly’. Do you feel the uncertainty about whetherbiology and physics can be naturally merged is gnawing away at you? Or, as he puts it in his opening sentences:

The subject of this book addresses basic questions that have transfixed and tormented humankind for millennia, ever since we sought to better understand our place in the universe – the nature of living things and their relationship to the non-living. The importance of finding a definitive answer to these questions cannot be overstated – it would reveal to us not just who and what we are, but would impact on our understanding of the universe as a whole. (p.viii)

I immediately disagreed. ‘The importance of finding a definitive answer to these questions cannot be overstated’? Yes it can. Maybe, just maybe – it is not very important at all.

What do we mean by ‘important’, anyway? Is it important to you, reading this review, to realise that the division between the initial, chemical phase of the origin of life and the secondary, biological phase, is in fact a delusion, and that both processes can be accounted for by applying Darwinian selection to supposedly inorganic chemicals?

If you tried to tell your friends and family 1. how easy would you find it to explain? 2. would you seriously expect anyone to care?

Isn’t it, in fact, more likely that the laws or rules or theories about how life arose from inanimate matter are likely to be so technical, so specialised and so hedged around with qualifications, that only highly trained experts can really understand them?

Maybe Pross has squared the circle and produced a feasible explanation of the origins of life on earth. Maybe this book really is – The Answer! But in which case – why hasn’t everything changed, why hasn’t the whole human race breathed a collective sigh of relief and said, NOW we understand how it all started, NOW we know what it all means, NOW I understand who I am and my place in the universe?

When I explained Pross’s theory, in some detail, to my long-suffering wife (who did a life sciences degree) she replied that, quite obviously chemistry and biology are related; anyone who’s studied biology knows it is based on chemistry. She hardly found it ‘an extraordinary connection’. When I raised it with my son, who is studying biology at university, he’d never heard of Pross or his theory.

So one’s final conclusion is that our understanding of ‘The nature of life, and hence man’s place in the universe’ has remained remarkably unchanged by this little book and will, in all likelihood, remain so.

Related links

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1 Comment
by Simon on April 17, 2019  •  Permalink
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Posted by Simon on April 17, 2019

https://astrofella.wordpress.com/2019/04/17/what-is-life-how-chemistry-becomes-biology-addy-pross/

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