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 biTotechnologist, 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 Continent and settled in Ireland. He 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. These are the lectures which 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).

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 12 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 namechecking 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 Watson’s book, 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 cells contain about a thousand ribosomes), and the role of messenger RNA in cutting off snippets of DNA and taking them to the ribosome. This is where transfer RNA (tRNA) then brings along amino acids which are 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.

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 useful protein again.

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 explains 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 explain how he led teams which looked into splicing one organism’s DNA into another. And then 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 into actual meetings where he and colleagues discuss how to tackle the whole series of technical problems they faced, and explain 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 texts he exchanged with colleagues (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 – in order to get to the actual outcomes. These 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 then, in the quest to create the first ever synthesised life form in chapter 8, ‘Synthesis of the M. mycoides genome’. More recently, after the timescale of 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. 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, reading them carefully, just how ethnically mixed the names are – Chinese, Indian, French, German, Spanish – names from all around the world. Without anyone having to explain it, 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, 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 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 builds up to the fact that Venter really has it in for 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, 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.

2. Creating life

The corollary of there being nothing magical about ‘life’ is the confident way Venter 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 he 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 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 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 Bellos and Stewart through the astrophysicists Hawking and Davies and 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 (thinking people are very bothered 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.

3. Public debate is often meaningless Worse, they believe that something called ‘education’ and ‘public debate’ will control the threat posed by these 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 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 may be 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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