Life At The Speed of Light: From the Double Helix to the Dawn of Digital Life by J. Craig Venter (2013)

The future of biological research will be based to a great extent on the combination of computer science and synthetic biology. (p.204)

Who is Craig Venter?

The quickest way of getting the measure of this hugely clever, ambitious and visionary man is to quote his Wikipedia entry:

John Craig Venter (born October 14, 1946) is an American biotechnologist, biochemist, geneticist, and businessman. He is known for leading the first draft sequence of the human genome and assembled the first team to transfect a cell with a synthetic chromosome. Venter founded Celera Genomics, The Institute for Genomic Research (TIGR) and the J. Craig Venter Institute (JCVI), where he currently serves as CEO. He was the co-founder of Human Longevity Inc. and Synthetic Genomics. He was listed on Time magazine’s 2007 and 2008 Time 100 list of the most influential people in the world. In 2010, the British magazine New Statesman listed Craig Venter at 14th in the list of ‘The World’s 50 Most Influential Figures 2010’. He is a member of the USA Science and Engineering Festival’s Advisory Board.

So he’s a heavy hitter, invited to Bill Clinton’s White House to announce his team’s successful sequencing of the first human genome on 2000, founder of a thriving biochem business, a number of charities, pioneer of genomics (‘the branch of molecular biology concerned with the structure, function, evolution, and mapping of genomes’) and mapper of an ambitious future for the new science of synthetic biology.

In Schrödinger’s footsteps

Life At The Speed of Light was published in 2013. It originated as a set of lectures. As he explains in the introduction, in 1943, the Austrian physicist Erwin Schrödinger had fled the Nazi-controlled Continent and settled in Ireland. Schrödinger was invited by the Taoiseach of the time to give some public lectures and chose the topic of life – the biology and physics of life. Schrödinger’s lectures were then published in the little book What Is Life? (1944) which inspired generations of young people to take up science (in his memoir The Double Helix James Watson describes how the book inspired him; Addy Pross named his book about the origins of life, What Is Life?, as a direct tribute to Schrödinger’s text).

Well, 49 years later Venter was invited by the Taoiseach of the day to deliver a new set of lectures, addressing the same question as Schrödinger, but in doing so, making clear the enormous strides in physics, chemistry, biology, biochemistry and genetics which had been made in that half-century.

Twelve chapters

The twelve chapters are titled:

  1. Dublin, 1943-2012
  2. Chemical synthesis as proof
  3. Dawn of the digital age of biology
  4. Digitizing life
  5. Synthetic Phi X 174
  6. First synthetic genome
  7. Converting one species into another
  8. Synthesis of the M. mycoides genome
  9. Inside a synthetic cell
  10. Life by design
  11. Biological transportation
  12. Life at the speed of light

Each chapter contains a formidable amount of state-of-the-art biochemical knowledge. The first few chapters recap relevant forebears who helped figure out that DNA was the vehicle of heredity, beginning right back at the start with Aristotle, who made the primal division of living things into animal, vegetable or mineral, and then going on to namecheck other pioneers such as Robert Hook and, of course, Charles Darwin.

Biochemistry

But the real thrust of the book is to get up to date with contemporary achievements in sequencing genomes and creating transgenic entities i.e. organisms which have had the DNA of completely separate organisms stitched into them.

In order to do this Venter, of course, has to describe the molecular mechanisms of life in great detail. Successive chapters go way beyond the simplistic understanding of DNA described in James Watson’s book about the double helix, and open up for the reader the fantastical fairyland of how DNA actually works.

He explains the central role of the ribosomes, which are the factories where protein synthesis takes place (typical human cells contain about a thousand ribosomes), and the role of messenger RNA in cutting off snippets of DNA and taking them to the ribosome.

It is to the ribosome that transfer RNA (tRNA) brings along amino acids, which are then intricately assembled according to the sequence of bases found on the original DNA. Combinations of the twenty amino acids are assembled into the proteins which all life forms are made of – from the proteins which make up the cell membrane, to collagen which accounts for a quarter of all the proteins found in vertebrate animals, or elastin, the basis of lung and artery walls, and so on and so on.

I found all this mind-boggling, but the most striking single thing I learned is how fast it happens, and that it needs to happen so unrelentingly.

Fast

Venter explains that protein synthesis requires only seconds to make chains of a hundred amino acids or more. Nowadays we understand the mechanism whereby the ribosome is able to ratchet RNAs laden with amino acids along its production lines at a rate of fifteen per second! Proteins need to ‘fold’ up into the correct shape – there are literally millions of possible shapes they can assume but they only function if folded correctly. This happens as soon as they’ve been manufactured inside the ribosome and takes place in a few thousandths of a second. The protein villin takes six millionths of a second to fold correctly!

I had no idea that some of the proteins required for life to function (i.e. for cells to maintain themselves) exist for as little as forty-five minutes before they decay and cease to work. Their components are then disassembled and returned to the hectic soup which is contained inside each cell membrane, before being picked up by passing tRNA and taken along to the ribosome to be packaged up into another useful protein.

Relentless

It is the absolutely relentless pressure to produce thousands of different proteins, on a continuous basis, never faltering, never resting, which makes the mechanisms of life so needy of resources, and explains why animals need to be constantly taking in nutrition from the environment, relentlessly eating, drinking, breaking food down into its elementary constituents and excreting waste products.

After a while the book began to make me feel scared by the awesome knowledge of what is required to keep ‘me’ going all day long. Just the sheer effort, the vast amount of biochemical activity going on in every one of the forty or so trillion cells which make up my body, gave me a sense of vertigo.

Every day, five hundred billion blood cells die in an individual human. It is also estimated that half our cells die during normal organ development. We all shed about five hundred million skin cells every day. As a result you shed your entire outer layer of skin every two to four weeks. (p.57 – my italics)

Life is a process of dynamic renewal.

In an hour or even less a bacterial cell has to remake all of its proteins or perish. (p.62)

Venter’s achievements

Having processed through the distinguished forebears and pioneers of biochemistry, Venter comes increasingly to the work which he’s been responsible for. First of all he describes the process behind the sequencing of the first human genome – explaining how he and his team devised a vastly faster method of sequencing than their rivals (and the controversy this aroused).

Then he goes on to tell how he led teams which looked into splicing one organism’s DNA into another. And then he explains the challenge of going to the next phase, and creating life forms from the DNA up.

In fact the core of the book is a series of chapters which describe in minute and, some might say, quite tedious detail, the precise strategies and methodologies Venter and his teams took in the decade or so from 2000 to 2010 to, as he summarises it:

  • synthesise DNA at a scale twenty times faster than previously possible
  • develop a methodology to transplant a genome from one species to another
  • solve the DNA-modification problems of restriction enzymes destroying transplanted DNA

Successive chapters take you right into actual meetings where he and colleagues discussed how to tackle the whole series of technical problems they faced, and explains in exquisite detail precisely the techniques they developed at each step of the way. He even includes work emails describing key findings or turning points, and the texts he exchanged with colleagues at key moments (pp.171-2).

After reading about a hundred of pages of this my mind began to glaze over and I skipped paragraphs and then pages which describe such minutiae as how he decided which members of the Institute to put in charge of which aspects of the project and why — because I was impatient to get to the actual outcomes. And these outcomes have been dramatic:

In May 2010, a team of scientists led by Venter became the first to successfully create what was described as ‘synthetic life’. This was done by synthesizing a very long DNA molecule containing an entire bacterium genome, and introducing this into another cell … The single-celled organism contains four ‘watermarks’ written into its DNA to identify it as synthetic and to help trace its descendants. The watermarks include:

    • a code table for entire alphabet, with punctuations
    • the names of 46 contributing scientists
    • three quotations
    • the secret email address for the cell.

Venter gives a detailed description of the technical challenges, and the innovations his team devised to overcome them, in the quest to create the first ever synthesised life form in chapter 8, ‘Synthesis of the M. mycoides genome’.

More recently, after the period covered by this book (although the book describes this as one of his goals):

On March 25, 2016 Venter reported the creation of Syn 3.0, a synthetic genome having the fewest genes of any freely living organism (473 genes). Their aim was to strip away all nonessential genes, leaving only the minimal set necessary to support life. This stripped-down, fast reproducing cell is expected to be a valuable tool for researchers in the field. (Wikipedia)

The international nature of modern science

One notable aspect of the text is the amount of effort he puts into crediting other people’s work, and in particular the way these consists of teams.

When Watson wrote his book he could talk about individual contributors like Linus Pauling, Maurice Wilkins, Oswald Avery, Erwin Chergaff or Rosalind Franklin. One of the many things that has changed since Watson’s day is the way science is now done by large teams, and often collaborations not only between labs, but between labs around the world.

Thus at every step of his explanations Venter is very careful indeed to give credit to each new insight and discovery which fed into his own team’s work, and to namecheck all the relevant scientists involved. It was to be expected that each page would be studded with the names of biochemical processes and substances, but just as significant, just as indicative of the science of our times, is the way each page is also freighted with lists of names – and also, just how ethnically mixed the names are – Chinese, Indian, French, German, Spanish – names from all around the world.

Without anyone having to explain it out loud, just page after page of the names alone convey what a cosmopolitan and international concern modern science is.

A simplified timeline

Although Venter spends some time recapping the steady progress of biology and chemistry into the 20th century and up to Watson and Crick’s discovery, his book really makes clear that the elucidation of DNA was only the beginning of an explosion of research into genetics, such that genetics – and the handling of genetic information – are now at the centre of biology.

1944 Oswald Avery discovered that DNA, not protein, was the carrier of genetic information
1949 Fred Sanger determined the sequence of amino acids in the hormone insulin

1950 Erwin Chargaff made the discoveries about the four components of DNA which became known as Chargaff’s Rules, i.e. the number of guanine units equals the number of cytosine units and the number of adenine units equals the number of thymine units, strongly suggesting they came in pairs
1952 the Miller-Urey experiments show that organic molecules could be created out of a ‘primal soup’ and electricity
1953 Watson and Crick publish structure of DNA
1953 Barbara McClintock publishes evidence of transposable elements in DNA, aka transposons or jumping genes
1955 Heinz Fraenkel-Conrat and biophysicist Robley Williams showed that a functional virus could be created out of purified RNA and a protein coat.
1956 Arthur Kornberg isolated the first DNA polymerizing enzyme, now known as DNA polymerase I

1961 Marshall Nirenberg and Heinrich J. Matthaei discover that DNA is used in sets of three called ‘codons’
1964 Robert Holley elucidates the structure of transfer RNA
1960s Werner Arber and Matthew Meselson isolate first restriction enzyme
1967 DNA ligase discovered, an enzyme capable of linking DNA into a ring such as is found in viruses
1967 Carl Woese suggests that RNA not only carries genetic information but has catalytic properties

1970 Hamilton O. Smith, Thomas Kelly and Kent Wilcox isolate the first type II restriction enzyme
1970 discovery of reverse transcriptase which converts RNA into DNA
1971 start if gene-splicing revolution when Paul Berg spliced part of a bacterial virus into a monkey virus
1972 Herbert Boyer splices DNA from Staphylococcus into E. Coli
1974 first transgenic mammal created by Rudolf Jaenisch and Beatrice Mintz
1974 development of ‘reverse genetics’ where you interefere with an organism’s DNA and see what happens
1976 first biotech company, Genentech, set up
1977 Boyer, Itakura and Riggs use recombinant DNA to produce a human protein
1977 Carl Woese proposes an entire new kingdom of life, the Archaea

1980 Charles Weissmann engineers the protein interferon using recombinant-DNA technology
1981 Racaniello and Baltimore used recombinant DNA technology to generate the first infectious clone of an animal RNA virus, poliovirus
1982 genetically engineered insulin becomes commercially available
1980s discovery of the function of proteasomes which break up unneeded or damaged proteins
1980s Ada Yonath and Heinz-Günter Wittman grow crystals from bacterial chromosomes
1985 Martin Caruthers and his team developed an automated DNA synthesiser
1985 Aaron Klug develops ‘zinc fingers’, proteins which bind to specific three-letter sequences of DNA

1996 proposed life on Mars on the basis of microbial ‘fossils’ found in rocks blown form Mars to earth – later disproved
1996 publication of the yeast genome
1997 Venter’s team publish the entire genome of the Helicobacter pylori bacterium
1997 Dolly the sheep is cloned (DNA from a mature sheep’s mammary gland was injected into an egg that had had its own nucleus removed; it was named Dolly in honour of Dolly Parton and her large mammary glands)
1998 Andrew Fire and Craig Cameron Mello showed that so-called ‘junk DNA’ codes for double stranded RNA which trigger or shut down other genes
1999 Harry F. Noller publishes the first images of a complete ribosome

2005 The structure and function of the bacterial chromosome by Thanbichler, Viollier and Shapiro
2007 publication of Synthetic Genomics: Options for Government
2008 Venter and team create a synthetic chromosome of a bacterium
2010 Venter’s team announce the creation of the first synthetic cell (described in detail in chapter 8)
2011 first structure of a eukaryotic ribosome published

Life at the speed of light

Anyway, this is a book with a thesis and a purpose. Or maybe two purposes, two sides of the same coin. One is to eradicate all irrational, magical beliefs in ‘vitalism’, to insist that life is nothing but chemistry. The other is for Venter to proclaim his bold visions of the future.

1. Anti-vitalism

The opening chapter had included a brief recap of the literature and fantasy of creating new life, Frankenstein etc. This turns out to be because Venter is a fierce critic of all traditions and moralists who believe in a unique life force. He is at pains to define and then refute the theory of vitalism – ‘the theory that the origin and phenomena of life are dependent on a force or principle distinct from purely chemical or physical forces.’ Venter very powerfully believes the opposite: that ‘life’ consists of information about chemistry, and nothing more.

This, I think, is a buried motive for describing the experiments carried out at his own institute in such mind-numbing detail. It is to drill home the reality that life is nothing more than chemistry and information. If you insert the genome of one species into the cells of another they become the new species. They obey the genomic or chemical instructions. All life does. There is no mystery, no vital spark, no élan vital etc etc.

A digression on the origins of life

This is reinforced in chapter 9 where Venter gives a summary of the work of Jack W. Szostak into the origin of life.

Briefly, Szostak starts with the fact that lipid or fat molecules are spontaneously produced in nature. He shows that these tend to link up together to form ‘vesicles’ which also, quite naturally, form together into water-containing membranes. If RNA – which has been shown to also assemble spontaneously – gets into these primitive ‘cells’, then they start working, quite automatically, to attract other RNA molecules into the cell. As a result the cell will swell and, with a little shaking from wind or tide, replicate. Voilà! You have replicating cells containing RNA.

Venter then describes work that has been done into the origin of multicellularity i.e. cells clumping together to co-operate, which appears to have happened numerous times in the history of life, to give rise to a variety of multicellular lineages.

Venter goes on to describe one other major event in the history of life – symbiogenesis – ‘The theory holds that mitochondria, plastids such as chloroplasts, and possibly other organelles of eukaryotic cells represent formerly free-living prokaryotes taken one inside the other in endosymbiosis.’

In other words, at a number of seismic moments in the history of life, early eukaryotic cells engulfed microbial species that were living in symbiosis with them. Or to put it another way, early cells incorporated useful microbes which existed in their proximity, entirely into themselves.

The two big examples are:

  • some two billion years ago, when a eukaryotic cell incorporated into itself a photosynthetic bacterial algae cell which ultimately became the ‘chloroplast‘ – the site where photosynthesis takes place – in all successive plant species
  • and the fact that the ‘power packs’ of human cells, known as mitochondria, carry their own genetic code and have their own way of reproducing, indicating that they were taken over whole, not melded or merged but swallowed (it is now believed that human mitochondria derived from a specific bacterium, Rickettsia, which survives down to this day)

This information is fascinating in itself, but it is clearly included to join up with the detailed description of the work in his own institute in order to make the overwhelming case that life is just information and that DNA is the bearer of that information.

It obviously really irritates Venter that, despite the overwhelming weight of the evidence, people at large – journalists, philosophers, armchair moralists and religious believers – refuse to accept it, refuse to face the facts, and still believe there is something special about life, that humans, in particular, have a soul or spirit or other voodoo codswallop.

2. Creating life

The corollary of Venter’s insistence that there being nothing magical about ‘life’, is the confident way he interprets all the evidence he has so painstakingly described, and all the dazzling achievements he has been involved in, as having brought humanity to the brink of a New Age of Life, a New Epoch in the Evolution of Life on Earth.

We have now entered what I call ‘the digital age of biology’, in which once distinct domains of computer codes and those that program life are beginning to merge, where new synergies are emerging that will drive evolution in radical directions. (p.2)

The fusion of the digital world of the machine and that of biology would open up the remarkable possibilities for creating novel species and guiding future evolution. (p.109)

In the final chapters of this book Venter waxes very lyrical about the fantastic opportunities opening up for designing DNA on computers, modeling the behaviour of this artificial DNA, fine-tuning the design, and then building new synthetic organisms in the real world.

The practical applications know no limits, and on page 221 he lists some:

  • man-made organisms which could absorb the global warming CO2 in the air, or eat oil pollution, turning it into harmless chemicals
  • computer designing cures for diseases
  • designing crops that are resistant to drought, that can tolerate disease or thrive in barren environments, provide rich new sources of protein and other nutrients, can be harnessed for water purification in arid regions
  • designing animals that become sources for pharmaceuticals or spare body parts
  • customising human stem cells to regenerate damaged organs and bodies

Biological transformations

The final two chapters move beyond even these sci-fi goals to lay out some quite mind-boggling visions of the future. Venter builds on his institute’s achievements to date, and speculates about the kinds of technologies we can look forward to or which are emerging even as he writes.

The one that stuck in my mind is the scenario that, when the next variety of human influenza breaks out, doctors will only have to get a sample of the virus to a lab like Venter’s and a) they will now be able to work out its DNA sequence more or less the same day b) they will then be able to design a vaccine in a computer c) they will be able to create the DNA they have designed in the lab much faster than ever possible before but d) they will be able to email the design for this vaccine DNA anywhere in the world, at the speed of a telephone wire, at the speed of light.

That is what the title of the book means. New designs for synthesised life forms can now be developed in computers (which are working faster and faster) and then emailed wherever they’re required i.e. to the centre of the outbreak of a new disease, where labs will be able to use the techniques pioneered by Venter’s teams to culture and mass produce vaccines at record speeds.


Scientific myopia

I hate to rain on his parade, but I might as well lay out as clearly as I can the reasons why I am not as excited about the future as Venter. Why I am more a J.G. Ballard and John Gray man than a Venter man.

1. Most people don’t know or care Venter takes the position of many of the scientists I’ve been reading – from the mathematicians Alex Bellos and Ian Stewart through to the astrophysicists Stephen Hawking and Paul Davies and Paul Barrow, to the origin-of-life men Cairns-Smith and Addy Pross – that new discoveries in their fields are earth-shatteringly important and will make ordinary people stop in their tracks, and look at their neighbour on the bus or train and exclaim, ‘NOW I understand it! NOW I know the meaning of life! NOW I realise what it’s all about.’

A moment’s reflection tells you that this simply won’t happen. Einstein’s relativity, Schrödinger and Bohr’s quantum mechanics, the structure of DNA, cloning, the discovery of black holes – what is striking is how little impact most of these ‘seismic’ discoveries have had on most people’s lives or thinking.

Ask your friends and family which of the epic scientific discoveries of the 20th century I’ve listed above has made the most impact on their lives. Or they’ve even heard of. Or could explain.

2. Most people are not intellectuals This error (the notion that ordinary people are excited about scientific ‘breakthroughs’) is based on a deeper false premise, one of the great category errors common to all these kind of books and magazine articles and documentaries – which is that the authors think that everyone else in society is a university-educated intellectual like themselves, whereas, very obviously, they are not. Trump. Brexit. Most people in western democracies are not university-educated intellectuals.

3. Public debate is often meaningless Worse, university-educated intellectuals have a bad habit of believing that something called ‘education’ and ‘public debate’ will control the threat posed by these new technologies:

Opportunities for public debate and discussion on this topic must be sponsored, and the lay public must engage with the relevant issues. (p.215)

Famous last words. Look at the ‘debate’ surrounding Brexit. Have any of the thousands of articles, documentaries, speeches, books and tweets helped solve the situation? No.

‘Debate’ hardly ever solves anything. Clear-cut and affordable solutions which people can understand and get behind solve things.

4. A lot of people are nasty, some are evil Not only this but Venter, like all the other highly-educated, middle-class, liberal intellectuals I’ve mentioned, thinks that people are fundamentally nice – will welcome their discoveries, will only use them for the good of mankind, and so on.

Megalolz, as my kids would say. No. People are not nice. The Russians and the Chinese are using the internet to target other countries’ vital infrastructures, and sow misinformation. Islamist warriors are continually looking for ways to attack ‘the West’, the more spectacular, the more deaths, the better. In 2010 Israel is alleged to have carried out the first cyberattack on another nation’s infrastructure when it (allegedly) attacked a uranium enrichment facility at Iran’s Natanz underground nuclear site.

In other words, cyberspace is not at all a realm where high-minded intellectuals meet and debate worthy moral issues, and where synthetic biologists devise life-saving new vaccines and beam them to locations of epidemic outbreaks ‘at the speed of light’. Cyberspace is already a war zone.

And it is a warzone in a world which contains some nasty regimes, not just those which are in effect dictatorships (Iran, China) but even many of the so-called democracies.

Trump. Putin. Erdogan. Bolsonaro. Viktor Orban. These are all right-wing demagogues who were voted into power in democratic elections.

It seems to me that both the peoples, and the leaders, who Venter puts his faith in are simply not up to the job of understanding, using wisely or safeguarding, the speed of light technology he is describing.

Venter goes out of his way, throughout the book, to emphasise how socially responsible he and his Institute and his research have been, how they have taken part in, sponsored and contributed to umpteen conferences and seminars, alongside government agencies like the FBI and Department of Homeland Security, into the ‘ethics’ of conducting synthetic biology (i.e. designing and building new organisms) and into its risks (terrorists use it to create lethal biological weapons).

Indeed, most of chapter ten is devoted to the range of risks – basically, terrorist use or some kind of accident – which could lead to the release of harmful, synthesised organisms into the environment – accompanied by a lot of high-minded rhetoric about the need to ‘educate the public’ and ‘engage a lay audience’ and ‘exchange views’, and so on…

I believe that the issue of the responsible use of science is fundamental… (p.215)

Quite. But then the thousands of scientists and technicians who invented the atom bomb were highly educated, highly moral and highly responsible people, too. But it wasn’t them who funded it, deployed it and pushed the red button. Good intentions are not enough.


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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.


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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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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.


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