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

Who is Craig Venter?

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

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

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

In Schrödinger’s footsteps

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

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

Twelve chapters

The twelve chapters are titled:

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

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

Biochemistry

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

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

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

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

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

Fast

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

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

Relentless

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

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

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

Life is a process of dynamic renewal.

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

Venter’s achievements

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

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

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

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

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

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

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

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

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

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

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

The international nature of modern science

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

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

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

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

A simplified timeline

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

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

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

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

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

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

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

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

Life at the speed of light

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

1. Anti-vitalism

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

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

A digression on the origins of life

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

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

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

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

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

The two big examples are:

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

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

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

2. Creating life

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

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

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

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

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

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

Biological transformations

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

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

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

Scientific myopia

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Related links

• Life at the Speed of Light: From the Double Helix to the Dawn of Digital Life on Amazon
• J. Craig Venter Institute website
• The International Genetically Engineered Machine competition

Reviews of other science books

Chemistry

• The Periodic Kingdom: A Journey Into the Land of the Chemical Elements by Peter Atkins (1995)

Cosmology

• The Perfect Theory by Pedro G. Ferreira (2014)
• The Book of Universes by John D. Barrow (2011)
• The Origin Of The Universe: To the Edge of Space and Time by John D. Barrow (1994)
• The Last Three Minutes: Conjectures about the Ultimate Fate of the Universe by Paul Davies (1994)
• A Brief History of Time: From the Big Bang to Black Holes by Stephen Hawking (1988)
• The Black Cloud by Fred Hoyle (1957)

The Environment

• The Sixth Extinction: An Unnatural History by Elizabeth Kolbert (2014)
• The Sixth Extinction by Richard Leakey and Roger Lewin (1995)

Genetics and life

• Life At The Speed of Light: From the Double Helix to the Dawn of Digital Life by J. Craig Venter (2013)
• What Is Life? How Chemistry Becomes Biology by Addy Pross (2012)
• Seven Clues to the Origin of Life by A.G. Cairns-Smith (1985)
• The Double Helix by James Watson (1968)

Human evolution

• The Origin of Our Species by Chris Stringer (2011)
• Guns, Germs and Steel by Jared Diamond (1997)

Maths

• Alex’s Adventures in Numberland by Alex Bellos (2010)
• Nature’s Numbers: Discovering Order and Pattern in the Universe by Ian Stewart (1995)
• Innumeracy: Mathematical Illiteracy and Its Consequences by John Allen Paulos (1988)
• A Mathematician Reads the Newspaper: Making Sense of the Numbers in the Headlines by John Allen Paulos (1995)

Particle physics

• Atomic by Jim Baggott (2009)

Psychology

• Tips For Trying To Think Less Irrationally
• Irrationality: The Enemy Within by Stuart Sutherland (1992)
• Judgement Under Uncertainty: Heuristics and Biases by Amos Tversky and Daniel Kahneman (1974)