All posts tagged Francis Crick

Seven Clues to the Origin of Life by A.G. Cairns-Smith (1985)

The topic of the origin of life on the Earth is a branch of mineralogy. (p.99)

How did life begin? To be more precise, how did the inorganic chemicals formed in the early years of planet earth, on the molten rocks or in the salty sea or in the methane atmosphere, transform into ‘life’ – complex organisms which extract food from the environment and replicate, and from which all life forms today are ultimately descended? What, when and how was that first momentous step taken?

Thousands of biologists have devoted their careers to trying to answer this question, with the result that there are lots of speculative theories.

Alexander Graham Cairns-Smith (1931-2016) was an organic chemist and molecular biologist at the University of Glasgow, and this 120-page book was his attempt to answer the Big Question.

In a nutshell he suggested that life derived from self-replicating clay crystals. To use Wikipedia’s summary:

Clay minerals form naturally from silicates in solution. Clay crystals, like other crystals, preserve their external formal arrangement as they grow, snap, and grow further.

Clay crystal masses of a particular external form may happen to affect their environment in ways that affect their chances of further replication. For example, a ‘stickier’ clay crystal is more likely to silt up a stream bed, creating an environment conducive to further sedimentation.

It is conceivable that such effects could extend to the creation of flat areas likely to be exposed to air, dry, and turn to wind-borne dust, which could fall randomly in other streams.

Thus – by simple, inorganic, physical processes – a selection environment might exist for the reproduction of clay crystals of the ‘stickier’ shape.

Cairns-Smith’s book is densely argued, each chapter like a lecture or seminar packed with suggestive evidence about what we know about current life forms, a summary of the principles underlying Darwin’s theory of evolution, and about how we can slowly move backwards along the tree of life, speculating about how it developed.

But, as you can see from the summary above, in the end, it is just another educated guess.

Detective story

The blurb on the back and the introduction both claim the book is written in the style of a detective story. Oh no it isn’t. It is written in the style of a biology book – more precisely, a biology book which is looking at the underlying principles of life, the kind of abstract engineering principles underlying life – and all of these take quite some explaining, drawing in examples from molecular biology where required.

Sometimes (as in chapter 4 where he explains in detail how DNA and RNA and amino acids and proteins interact within a living cell) it becomes quite a demanding biology book.

What the author and publisher presumably mean is that, in attempt to sweeten the pill of a whole load of stuff about DNA and ribosomes, Cairns-Smith starts every chapter with a quote from a Sherlock Holmes story and from time to time claims to be pursuing his goal with Holmesian deduction.

You see Holmes, far from going for the easy bits first, would positively seek out those features in a case that were seemingly incomprehensible – ‘singular’ features he would call them… I think that the origin of life is a Holmesian problem. (p.ix)

Towards the very end, he remembers this metaphor and talks about ‘tracking down the suspect’ and ‘making an arrest’ (i.e. of the first gene machine, the origin of life). But this light dusting of Holmesiana doesn’t do much to conceal the sometimes quite demanding science, and the relentlessly pedagogical tone of the book.

Broad outline

1. Panspermia

First off, Cairns-Smith dismisses some of the other theories about the origin of life. He makes short work of the theories of Fred Hoyle and Francis Crick that organic life might have arrived on earth from outer space, carried in dust clouds or on meteors etc (Crick’s version of this was named ‘Panspermia’) . I agree with Cairns-Smith that all variations on this hypothesis just relocate the problem somewhere else, but don’t solve it.

Cairns-Smith states the problem in three really fundamental facts:

  1. There is life on earth
  2. All known living things are at root the same (using the same carbon-based energy-gathering and DAN-replicating biochemistry)
  3. All known living things are very complicated

2. The theory of chemical evolution

In his day (the 1970s and 80s) the theory of ‘chemical evolution’ was widely thought to address the origin of life problem. This stated that lot of the basic amino acids and sugars which we find in organisms are relatively simple and so might well have been created by accident in the great sloshing oceans and lakes of pre-life earth, and that they then – somehow – came together to make more complex molecules which – somehow – learned how to replicate.

But it’s precisely on the vagueness of that ‘somehow’ that Cairns-Smith jumps. The leap from a random soup of semi-amino acids washing round in a lake and the immensely detailed and complex machinery of life demonstrated by even a tiny living organism – he selects the bacterium Escherichia coli – is just too vast a cliff face to have been climbed at random, by accident. It’s like saying if you left a bunch of wires and bits of metal sloshing around in a lake long enough they would eventually make a MacBook Air.

Cairns-Smith zeroes in on four keys aspects of life on earth which help to disprove the ‘chemical evolution’ theory.

  1. Life forms are complex systems. It is the whole machine which makes sense of its components.
  2. The systems are highly interlocked: catalysts are needed to make proteins, but proteins are needed to make catalysts; nucleic acids are needed to make proteins, yet proteins are needed to make nucleic acids;
  3. Life forms are very complex.
  4. The system is governed by rules and conventions: the exact choice of the amino acid alphabet and the set of assignments of amino acid letters to nucleic acid words are examples.

3. The Miller-Urey experiments

Cairns-Smith then critiques the theory derived from the Miller-Urey experiments.

In 1953 a graduate student, Stanley Miller, and his professor, Harold Urey, performed an experiment that demonstrated how organic molecules could have spontaneously formed from inorganic precursors, under conditions like those posited by the Oparin-Haldane Hypothesis. The now-famous ‘Miller–Urey experiment’ used a highly reduced mixture of gases – methane, ammonia and hydrogen – to form basic organic monomers, such as amino acids. (Wikipedia)

Cairns-Smith spends four pages comprehensively demolishing this approach by showing that:

  1. the ultraviolet light its exponents claim could have helped synthesise organic molecules is in fact known to break covalent bonds and so degrade more than construct complex molecules
  2. regardless of light, most organic molecules are in fact very fragile and degrade easily unless kept in optimum conditions (i.e. inside a living cell)
  3. even if some organic molecules were created, organic chemists know only too well that there are hundreds of thousands of ways in which carbon, hydrogen, nitrogen and oxygen can combine, and most of them result in sticky sludges and tars in which nothing could ‘live’

So that:

  1. Only some of the molecules of life can be made this way
  2. Most of the molecules that would be made this way are emphatically not the ‘molecules of life’
  3. The ‘molecules of life’ are usually better made under conditions far most favourable than those obtaining back in the primordial soup era

He then does some back-of-a-matchbox calculations to speculate about how long it would take a random collection of organic molecules to ‘happen’ to all tumble together and create a life form: longer than the life of the universe, is his conclusion. No, this random approach won’t work.

Preliminary principles

Instead, he suggests a couple of principles of his own:

  1. That some and maybe all of the chemicals we now associate with ‘life’ were not present in the first replicating organisms; they came later; their exquisitely delicate interactivity suggests that they are the result not the cause of evolution
  2. Therefore, all lines of investigation which seek to account for the presence of the molecules of life are putting the cart before the horse: it isn’t the molecules which are important – it is the mechanism of replication with errors

Cairns-Smith thinks we should put the molecules of life question completely to one side, and instead seek for entirely inorganic systems which would replicate, with errors, so that the errors would be culled and more efficient ways of replicating tend to thrive on the available source material, beginning to create that dynamism and ‘sense of purpose’ which is one of life’s characteristics.

We keep coming to this idea that at some earlier phase of evolution, before life as we know it, there were other kinds of evolving system, other organisms that, in effect, invented our system. (p.61)

This seems, intuitively, like a more satisfying approach. Random forces will never make a MacBook Air and, as he has shown in chapter 4, even an entity like Escherichia coli is so staggeringly complex and amazingly finely-tuned as to be inconceivable as the product of chance.

Trying to show that complex molecules like ribosomes or RNA or amino acids – which rely on each other to be made and maintained, which cannot exist deprived of the intricately complicated interplay within each living cell – came about by chance is approaching the problem the wrong way. All these complex organic molecules must be the result of evolution. Evolution itself must have started with something much, much simpler – with the ‘invention’ of the basic engine, motor, the fundamental principle – and this is replication with errors. In other words:

Evolution started with ‘low-tech’ organisms that did not have to be, and probably were not made from, ‘the molecules of life’. (p.65)

Crystals

And it is at this point that Cairns-Smith introduces his Big Idea – the central role of clay crystals – in a chapter titled, unsurprisingly, ‘Crystals’ (pp.75-79).

He now explains in some detail the surprisingly complicated and varied world of clay crystals. These naturally form in various solutions and, if splashed up onto surfaces like rocks or stones, crystallise out into lattices, but the crystallisation process also commonly involves errors and mutations.

His description of the different types of crystals and their properties is fascinating – who knew there were so many types, shapes, patterns and processes, starting with an introduction to the processes of saturation and super-saturation. The point is that crystals naturally occur and naturally mutate. He lists the ways they can vary or diverge from their ‘pure’ forms: twinning, stacking errors, cation substitutions, growth in preferred directions, break-up along preferred planes (p.97).

There follows a chapter about the prevalence of crystals in mud and clay and, therefore, their widespread presence in the conditions of the early planet earth.

And then, finally, he explains the big leap whereby replicating crystals may have attracted to themselves other molecules.

There follows a process of natural selection for clay crystals that trap certain forms of molecules to their surfaces that may enhance their replication potential. Complex proto-organic molecules can be catalysed by the surface properties of silicates.

Genetic takeover of the crystals

It is at this point that he introduces the idea of a ‘genetic takeover’.

When complex molecules perform a ‘genetic takeover’ from their clay ‘vehicle’, they become an independent locus of replication – an evolutionary moment that might be understood as the first exaptation.

(Exaptation = ‘the process by which features acquire functions for which they were not originally adapted or selected’)

Cairns-Smith had already described this process – the ‘genetic takeover’ of an initial, non-organic process by more complex, potentially organic molecules – in his earlier, longer and far more technical book, Genetic Takeover: And the Mineral Origins of Life, published in 1982.

This book – the Seven Clues – is a much shorter, non-technical and more accessible popularisation of the earlier tome. Hence the frivolous references to Sherlock Holmes.

Proliferating crystals form the scaffold for molecules which learn to replicate without them

The final chapter explains how these very common and proliferating entities (clay crystals) might have formed into structures and arrangements which attracted – for purely chemical reasons – various elementary organic molecules to themselves.

Certain repeating structures might attract molecules which then build up into more complex molecules, into molecules which are more efficient at converting the energy of the sun into further molecular combinations. And thus the principle of replication with variation, and competition for resources among the various types of replicating molecule, would have been established.

Thoughts

At this point the book ends, his case presented. It has been a fascinating journey because a) it is interesting to learn about all the different shapes and types of clay crystal b) he forces the reader to think about the fundamental engineering and logistical aspects of life forms, to consider the underlying principles which must inform all life forms, which is challenging and rewarding.

But, even in his own terms, Cairns-Smith’s notion of more and more complex potentially organic molecules being haphazardly replicated on a framework of proliferating clay crystals is still a long, long, long way from even the most primitive life forms known to us, with their vastly complex structure of cell membrane, nucleus and internal sea awash with DNA-controlled biochemical processes.

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1 Comment
by Simon on April 16, 2019  •  Permalink
Posted in Books, Chemistry, Science
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Posted by Simon on April 16, 2019

https://astrofella.wordpress.com/2019/04/16/seven-clues-to-the-origin-of-life-a-g-cairns-smith/

The Double Helix by James Watson (1968)

The short paper by James Watson and Francis Crick establishing the helical structure of the DNA molecule was published in the science journal, Nature, on April 25, 1953. The blurb of this book describes it as the scientific breakthrough of the 20th century. Quite probably, although it was a busy century – the discovery of antibiotics was quite important, too, not to mention the atom bomb.

James Watson and Francis Crick with their DNA model at the Cavendish Laboratories in 1953

Anyway, what makes this first-person account of the events leading up to the discovery such fun is Watson’s prose style and mentality. He is fearless. He takes no prisoners. He is brutally honest about his own shortcomings and everyone else’s and, in doing so, sheds extraordinarily candid light on how science is actually done. He tells us that foreign conferences where nobody speaks English are often pointless. Many scientists are just plain stupid. Some colleagues are useless, some make vital contributions at just the right moment.

Watson has no hesitation in telling us that, when he arrived in Cambridge in 1951, aged just 23, he was unqualified in almost every way – although he had a degree from the University of Chicago, he had done his best to avoid learning any physics or chemistry, and as a graduate student at Indiana he had also avoided learning any chemistry. In fact the book keeps referring to his astonishing ignorance of almost all the key aspects of the field he was meant to be studying.

The one thing he did have was a determination to solve the problem which had been becoming ever-more prominent in the world of biology, what is a gene? Watson says he was inspired by Erwin Schrödinger’s 1946 book, What Is Life? which pointed out that ‘genes’ were the key component of living cells and that, to understand what life is, we must understand what genes are and how they work. The bacteriologist O.T. Avery had already shown that hereditary traits were passed from one bacterium to another by purified DNA molecules, so this much was common knowledge in the scientific community.

DNA was probably the agent of hereditary traits, but what did it look like and how did it work?

Our hero gets a U.S. government research grant to go to Copenhagen to study with biochemist Herman Kalckar, his PhD supervisor Salvador Luria hoping the Dane would teach him something but… no. Watson’s interest wasn’t sparked, partly because Kalckar was working on the structure of nucleotides, which young Jim didn’t think were immediately relevant to his quest, also because Herman was hard to understand –

At times I stood about nervously while Herman went through the motions of a biochemist, and on several days I even understood what he said. (p.34)

A situation compounded when Herman began to undergo a painful divorce and his mind wandered from his work altogether.

It was a chance encounter at a conference in Naples that motivated Watson to seek out the conducive-sounding environment of Cambridge (despite the reluctance of his funding authorities back in the States to let him go so easily). John Kendrew, the British biochemist and crystallographer, at that point studying the structure of myoglobin, helped smooth his passage to the fens.

Head of the Cavendish Laboratory in Cambridge where Watson now found himself was Sir Lawrence Bragg, Nobel Prize winner and one of the founders of crystallography. The unit collecting X-ray diffraction photographs of haemoglobin was headed up by the Austrian Max Perutz, and included Francis Crick, at this stage (in 1951) 35-years-old and definitely an acquired taste. Indeed the famous opening sentence of the book is:

I have never seen Francis Crick in a modest mood.

followed by the observation that:

he talked louder and faster than anybody else, and when he laughed, his location within the Cavendish was obvious.

So he had found a home of sorts and, in Francis Crick, a motormouth accomplice who was also obsessed by DNA – but there were two problems.

  1. The powers that be didn’t like Crick, who was constantly getting into trouble and nearly got thrown out when he accused the head of the lab, Bragg, of stealing one of his ideas in a research paper.
  2. Most of the work on the crystallography of DNA was being done at King’s College, London, where Maurice Wilkins had patiently been acquiring X-rays of the molecule for nearly ten years.

There was a sub-problem here which was that Wilkins was being forced to work alongside Rosalind Franklin, an expert in X-ray crystallography, who was an independent-minded 31-year-old woman (b.1920) and under the impression that she had been invited in to lead the NA project. The very young Watson and the not-very-securely-based Crick both felt daunted at having to ask to borrow and interpret Wilkins’s material, not least because he himself would have to extract it from the sometimes obstreperous Franklin.

And in fact there was a third big problem, which was that Linus Pauling, probably the world’s leading chemist and based at Cal Tech in the States, was himself becoming interested in the structure of DNA and the possibility that it was the basis of the much-vaunted hereditary material.

Pauling’s twinkling eyes and dramatic flair when making presentations is vividly described (pp.37-8). Along the same lines, Watson later gives a deliberately comical account of how he is scoffed and ignored by the eminent biochemist Erwin Chargaff after making some (typically) elementary mistakes in basic chemical bonding.

It is fascinating to read the insights scattered throughout the book about the relative reputations of the different areas of science – physics, biology, biochemistry, crystallography and so on. Typical comments are:

  • ‘the witchcraft-like techniques of the biochemist’, p.63
  • ‘In England, if not everywhere, most botanists and zoologists were a muddled lot.’ p.63

In a typical anecdote, after attending a lecture in London given by Franklin about her work, Watson goes for a Chinese meal in Soho with Maurice Wilkins who is worried that he made a mistake moving into biology, compared to the exciting and well-funded world of physics.

The physics of the time was dominated by the aftershock of the massive wartime atom bomb project, and with ongoing work to develop both the H-bomb and peacetime projects for nuclear power.

During the war Wilkins had helped to develop improved radar screens at Birmingham, then worked on isotope separation at the Manhattan Project at the University of California, Berkeley. Now he was stuck in a dingy lab in King’s College arguing with Franklin almost every day about who should use the best samples of DNA and the X-ray equipment and so on. (Later on, Watson tells us Wilkins’ and Franklin’s relationship deteriorated so badly that he (Watson) was worried about lending the London team the Cambridge team’s wire models in case Franklin strangled Wilkins with them. At one point, when Watson walks in on Franklin conducting an experiment, she becomes so angry at him he is scared she’s going to attack him. Wilkins confirms there have been occasions when he has run away in fear of her assaulting him.)

It’s in this respect – the insights into the way the lives of scientists are as plagued by uncertainty, professional rivalry, and doubts about whether they’re in the right job, or researching the right subject, gnawing envy of more glamorous, better-funded labs and so on – that the book bursts with insight and human interest.

Deoxyribonucleic acid

By about page 50 Watson has painted vivid thumbnail portraits of all the players involved in the story, the state of contemporary scientific knowledge, and the way different groups or individuals (Wilkins, Franklin, Pauling, Crick and various crystallographer associates at the Cavendish) are all throwing around ideas and speculations about the structure of DNA, on bus trips, in their freezing cold digs, or over gooseberry pie at their local pub, the Eagle in Cambridge (p.75).

For the outsider, I think the real revelation is learning how very small the final achievement of Crick and Watson seems. Avery had shown that DNA was the molecule of heredity. Chergaff had shown it contained equal parts of the four bases. Wilkins and Franklin had produced X-ray photos which strongly hinted at the structure and the famous photo 51 from their lab put it almost beyond doubt that DNA had a helix structure. Pauling, in America, had worked out the helical structure of other long proteins and had now began to speculate about DNA (although Watson conveys his and Crick’s immense relief that Pauling’s paper on the subject, published in early 1953, betrayed some surprisingly elementary mistakes in its chemistry.) But the clock was definitely ticking very loudly, rivals were closing in on the answer, and the pages leading up to the breakthrough are genuinely gripping.

In other words, the final deduction of the double helix structure doesn’t come out of the blue; the precise opposite; from Watson’s account it seems like it would have only been a matter of time before one or other of these groups had stumbled across the correct structure.

But it is very exciting when Watson comes into work one day, clears all the clutter from his desk and starts playing around with pretty basic cardboard cutouts of the four molecules which, by now, had become strongly associated with DNA, adenine and guanine, cytosine and thymine.

Suddenly, in a flash, he sees how they assemble the molecules naturally arrange themselves into pairs linked by hydrogen bonds – adenine with thymine and cytosine with guanine.

For a long time they’d been thinking the helix had one strand at the core and that the bases stuck out from it, like quills on a porcupine. Now, in a flash, Watson realises that the the base pairs, which join together so naturally, form a kind of zip, and the bands of sugar-phosphates holding the thing together run along the outside – creating a double helix shape.

The structure of the DNA double helix. The atoms in the structure are colour-coded by element and the detailed structures of two base pairs are shown in the bottom right. (Source: Wikipedia)

Conclusion

I am not qualified to summarise the impact of the discovery of DNA has had on the world. Maybe it would take books to do so adequately. I’ll quote the book’s blurb:

By elucidating the structure of DNA, the molecule underlying all life, Francis Crick and James Watson revolutionised biochemistry. At the time, Watson was only 24. His uncompromisingly honest account of those heady days lifts the lid on the real world of great scientists, with their very human faults and foibles, their petty rivalries and driving ambition. Above all, he captures the extraordinary excitement of their desperate efforts to beat their rivals at King’s College to the solution to one of the great enigmas of the life sciences.

The science is interesting, but has been overtaken and superseded generations ago. It’s the characters and the atmosphere of the time (the dingy English rooms with no heating, the appalling English food), the dramatic reality of scientific competition, and then the genuinely exciting pages leading up to the breakthrough which makes Watson’s book such a readable classic.

Rosalind Franklin

I marked all the places in the text where a feminist might explode with anger. Both Watson, but even more Crick, assume pretty young girls are made for their entertainment. They are referred to throughout as ‘popsies’ and Crick in particular, although married, betrays an endless interest in the pretty little secretaries and au pairs which adorn Cambridge parties.

It is through this patronising and sexist prism that the pair judged the efforts of Franklin who was, reasonably enough, a hard-working scientist not at all interested in her appearance or inclined to conform to gender stereotypes of the day. She felt marginalised and bullied at the King’s College lab, and irritated by the ignorance and superficiality of most of Watson and Crick’s ideas, untainted as they were by any genuine understanding of the difficult art of X-ray crystallography – an ignorance which Watson, to his credit, openly admits.

Eventually, Franklin found working with Wilkins so intolerable that she left to take up a position at Birkbeck College and then, tragically, discovered she had incurable cancer, although she worked right up to her death in April 1958.

Franklin has become a feminist heroine, a classic example of a woman struggling to make it in a man’s world, patronised by everyone around her. But if you forget her gender and just think of her as the scientist called Franklin, it is still a story of misunderstandings and poisonous professional relations such as I’ve encountered in numerous workplaces. Watson and Crick’s patronising tone must have exacerbated the situation, but the fundamental problem was that she was given clear written instructions that she would be in charge of the X-ray crystallography at King’s College but then discovered that Wilkins thought he had full control of the project. This was a management screw-up more than anything else.

It does seem unfair that she wasn’t cited in the Nobel Prize which was awarded to Crick, Watson and Wilkins in 1962, but then she had died in 1958, and the Swedish Academy had a simple rule of not awarding the prize to dead people.

Still, it’s not like her name has disappeared from the annals of history. Quite the reverse:

Impressive list, don’t you think?

And anyone who hasn’t read the book might be easily persuaded that she was an unjustly victimised, patronised and ignored figure. But just to set the record straight, Watson chooses to end the entire book not with swank about his and Crick’s later careers, but with a tribute to Franklin’s character and scientific achievement.

In 1958, Rosalind Franklin died at the early age of thirty-seven. Since my initial impressions of her, both scientific and personal (as recorded in the early pages of this book), were often wrong, I want to say something here about her achievements. The X-ray work she did at King’s is increasingly regarded as superb. The sorting out of the A and B forms [of DNA], by itself, would have made her reputation; even better was her 1952 demonstration, using Patterson superposition methods, that the phosphate groups must be on the outside of the DNA molecule. Later, when she moved to Bernal’s lab, she took up work on tobacco mosaic virus and quickly extended our qualitative ideas about helical construction into a precise quantitative picture, definitely establishing the essential helical parameters and locating the ribonucleic chain halfway out from the central axis.

Because I was then teaching in the States, I did not see her as often as did Francis, to whom she frequently came for advice or when she had done something very pretty, to be sure he agreed with her reasoning. By then all traces of our early bickering were forgotten, and we both came to appreciate greatly her personal honesty and generosity, realising years too late the struggles that the intelligent woman faces to be accepted by a scientific world which often regards women as mere diversions from serious thinking. Rosalind’s exemplary courage and integrity were apparent to all when, knowing she was mortally ill, she did not complain but continued working on a high level until a few weeks before her death. (p.175)

That is a fine, generous and moving tribute, don’t you think? And as candid and honest as the rest of the book in admitting his and Crick’s complete misreading of her situation and character.

In a literal sense the entire book leads up to this final page [these are the last words of the book] and this book became a surprise bestseller and the standard source to begin understanding the events surrounding the discovery. So it’s hard to claim that her achievement was ‘suppressed’ or ‘ignored’ when this is the climax of the best-selling account of the story.

Related links

Reviews of other science books

Chemistry

Cosmology

The Environment

Genetics and life

Human evolution

Maths

Particle physics

Psychology

1 Comment
by Simon on April 15, 2019  •  Permalink
Posted in Biology, Books, Chemistry, Science
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Posted by Simon on April 15, 2019

https://astrofella.wordpress.com/2019/04/15/the-double-helix-james-watson/

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