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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The Double Helix by James Watson (1968)

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

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

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

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

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

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

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

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

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

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

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

I have never seen Francis Crick in a modest mood.

followed by the observation that:

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

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

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

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

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

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

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

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

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

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

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

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

Deoxyribonucleic acid

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

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

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

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

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

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

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

Conclusion

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

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

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

Rosalind Franklin

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

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

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

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

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

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

Impressive list, don’t you think?

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

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

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

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

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


Related links

Reviews of other science books

Chemistry

Cosmology

The Environment

Genetics and life

  • What Is Life? How Chemistry Becomes Biology by Addy Pross (2012)
  • The Diversity of Life by Edward O. Wilson (1992)
  • Seven Clues to the Origin of Life by A.G. Cairns-Smith (1985)
  • The Double Helix by James Watson (1968)

Human evolution

Maths

Particle physics

Psychology

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