The past and future of DNA

Review of ‘Creation’, by Adam Rutherford, published by Viking/Penguin

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This book is divided into two sections, printed upside down and back to back. It is a neat little trick which I don’t think I’ve come across before. There’s a good reason too: one half of the book is about the past history of life – looking specifically at the evolutionary history of DNA – while the other half is about the future, and how humans are now changing the rules via synthetic biology and genetic engineering. So you turn the book over at a time according roughly to the present.

Update: it’s even cleverer than I thought – the book is designed to mimic the structure of DNA itself, as was pointed out in this tweet:

So there you go. That one was lost on me.

Anyway, the only problem is reading in public, where you look like an idiot reading a book upside down. And I don’t know how it works on the Kindle version – I was kindly sent a hard copy by the author. Anyway, I’ll divide up this review also into two parts, to respect and follow the order of the book. The author Adam Rutherford by the way has very impressive credentials: he is both an evolutionary biologist and a geneticist, as well as being an editor at the prestigious scientific journal Nature. Visit his website for more.

Part One

It is fair to say that the precise origins of DNA remain somewhat obscure. We may never know exactly how the various elements – oxygen, carbon, nitrogen, hydrogen and phosphorus – first combined into this extraordinarily long self-replicating molecule. But, following on from Darwin’s famous speculation about life originating in some “warm little pond”, Rutherford does a pretty good job of conjuring up the likely situation, some time around 3.5 billion years ago.

There is much here to be amazed about here, but what I find most amazing is that it seems near-certain that life appeared on Earth only once. All living organisms – animals, plants, fungi, bacteria and archaea – all share fundamental characteristics that are extremely unlikely to have arisen independently. As well as DNA, these include RNA and cells, as well as some shared ‘organelles’ within cells. All life, therefore, is composed of cells that have divided from previous cells, right the way back through time to the ‘last universal common ancestor’, or Luca.

But where did Luca come from? The theory of panispernia, that life arrived from outer space, seems highly unlikely – there isn’t a shred of evidence for it, and anyway this would merely pass the buck to the same mystery further away. As early as the 1950s it was demonstrated that amino acids – the building blocks of all-important proteins – could be spontaneously assembled out of the right chemical soup in the presence of heat and electricity. But that turns out to be the easy bit.

The exploration is additionally complicated by the fact that life itself is notoriously difficult to define. Rutherford points out – quoting a famous court judgement on pornography – that we all ‘know it when we see it’, but in biological terms there is no clear dividing line. The cell is clearly alive, in that it replicates, excretes, is animate and so on, but its constituents – even including DNA – are merely chemical assemblages. This is a mystery embodied in all of us: we are all just collections of different molecules, but somehow we are also much more than that.

At the heart of the mystery lies DNA. I am ashamed to say that like many people I don’t think I really properly understood until comparatively recently that DNA is a universal code. Without knowing too much about it, I guess I thought that fish DNA was fishy, and strawberry DNA was, well, strawberry-y. But it isn’t. It’s all the same. The closest analogy is with Lego, where the building blocks are not nobbly bits of plastic but the nucleotides known by their letters A, T, G and C. These only pair one-way, A with T and G with C. Each ‘base pair’ forms a rung on the famous twisted ladder of the DNA double-helix.

How it all works is a little bit complicated, but the basics can be understood by anyone (even me). Rutherford does a fantastic job of explaining it, and making the process interesting. For recall purposes, readers might combine ‘Creation’ with the equally useful ‘Molecular Biology for Dummies’ – I find things are easier to remember if you get them explained twice, and differently. (There’s nothing dumb about the latter book by the way – it is delicously complicated in parts.)

Anyway, the essential thing to remember is that the sequence of DNA bases represents a code, which is read in the cell and used to produce proteins or perform other functions. Specific DNA sequences, which might be a few thousand base-pairs long, together comprise a gene, just like letters in this English alphabet combine in different sequences to form words. Most genes we are interested in encode for proteins, which then perform a specific function within or between cells. (This is done indirectly, via RNA, but I’ll leave it to Rutherford to explain it better than I ever could.) This is a simplification, as much of the DNA code is about which genes are switched on and off and ‘functional’ stuff like that.

DNA serves another essential purpose, which is to replicate itself. Each cell nucleus contains an entire copy of all your DNA – and when the time comes for that cell to split, the rungs of the entire double-helix ladder are unstitched like a zipper. Then, because each base letter only pairs with one other, the two halves can be reassembled into two entirely new DNA strands. It’s an extremely clever system, especially given that many organisms, ourselves included, have genomes which are at least a couple of billion base-pairs long. Which brings us back to the original question of how on Earth DNA first came about.

Well… I’m not going to spoil Rutherford’s story by attempting to summarise it here. Suffice to say that it likely involves RNA as a precursor, and may well have been so fantastically improbable that it qualifies for one of Douglas Adams’s Infinite Improbability spaceship drives, which at least explains why it only happened once. This might also mean that we are alone in the entire Universe, which otherwise seems equally improbable when you think about it.

Part 2

Over the last couple of hundred thousand years, along came Homo sapiens. Everything about our biology, as with all other living organisms, is a product of Darwinian natural selection, acting on our ancestors over billions of years. The unit of selection, remember, is not the individual organism or the species, but the gene, as Richard Dawkins was the first to popularise back in 1976 in The Selfish Gene. This is also quite interesting – it means that the unit of natural selection which generated our species and all others is not in itself actually alive, but merely a scrap of information.

Either way, it made humans, and we are fantastically clever. Clever enough, in fact, that we are the first species to evolve on this planet which had the intelligence to figure out how evolution worked. (And Charles Darwin, as Rutherford points out, was the first individual of our species who had that brilliant insight.) We now know also – though not entirely – how DNA works, and how genes function, enough to start playing around with them. This is the ‘Creation’ of the second half of Rutherford’s book, with ourselves in the driving seat as the creators. (I used the term ‘God Species’ in my own recent book partly for this same reason.)

Tinkering with genes, it turns out, is surprisingly easy. You get a ‘restriction enzyme’ to snip the DNA at the beginning and end of the genetic sequence you want, and the rest is a slightly more difficult version of Microsoft Word’s cut and paste. Once the new gene is in the target organism’s genome, delivered by a helpfully-engineered bacteria, perhaps, or a tiny particle of gold, it gets integrated into the DNA and begins doing its job like any other. An example Rutherford quotes is the production of spider silk in the milk of genetically-engineered goats, but there are of course hundreds of others, mostly in plants and microbes.

The creation of classic ‘GMOs’ is now established science, of course, despite the best efforts of the antis over many years. Rutherford is mainly concerned with the next biological frontier, which is synthetic biology – the use of DNA to perform a multitude of different tasks in a multitude of different organisms, some of them created specifically for this purpose. The best-known is Craig Venter’s pioneering synthetic bacterium Mycoplasma mycoides JCVI-syn1.0, the first living organism since the origin of life not to have a biological parent, which instead had its several hundred genes produced initially via software on a computer. (It wouldn’t be quite right to credit Venter’s team with creating the first organism without a cellular parent as the genome was implanted into an exising bacterial cell with its nucleus removed.)

Clearly synthetic biology can do an incredible amount of good. It may help cure genetic diseases, or at least eliminate their symptoms, and those of other common ailments like diabetes. It may even yield some significant gains in the ever-present battle against cancer, if organisms can be programmed to destroy those mutant cells which have themselves somehow eliminated their own genetically-programmed instructions for destruction. (Cancer happens when cells with damaged DNA ignore instructions for their own death and proliferate uncontrollably into tumours.) Instead of the blunt weapons of radio- and chemotherapy we may then have a therapy which works at source at the level of each individual cancer cell.

But synthetic biology, by dint of its very power and usefulness, could also conceivably be dual-purpose and used to do harm. Clearly it is already possible either to construct novel or long-vanished pathogens like smallpox, or to programme existing ones like flu to become both more deadly and more infectious. No-one, least of all the scientists involved, argues that synthetic biology should be unregulated. The challenge is to regulate it enough to stop misuse without strangling it entirely and forgoing its very obvious potential benefits, which may turn out to yield our greatest prospects for health and environmental progress over the coming century.

There is nothing new about this challenge – it has been inherent in every new technology which has had a transformative impact. Ammonia, produced for plant fertiliser without which more than half of humanity would starve, was originally synthesised for explosives in Germany and used extensively in the First World War. Many technologies are in their use both helpful and harmful: electricity is exceedingly useful around the home and exceedingly dangerous if you happen to put yourself in the way of receiving a strong electric current.

Clearly the antis who argue for bans and moratoriums are wrong. But where should the line be drawn? Rutherford tells the story of the two recent Science and Nature papers about enhanced flu viruses, which raised fears that potential bioterrorists might be armed with new information. On the other side is a whole open-source ‘garage biotech’ movement where biologically-inclined geeks the world over trade genes and genetic information via the internet in constructing their own creations. One of them might turn bad. Or one of them might cure cancer, or engineer a micro-organism which can successfully synthesise biodiesel for aircraft without using up a whole lot of land.

The debate will no doubt be messy, inconclusive and protracted, but Rutherford hopes, as do I, that it will at least be democratic. But for society to properly debate the merits of synthetic biology more people need to understand it – and for that purpose Rutherford’s book is a masterful and extremely valuable contribution. I highly recommend it.

3 comments

  1. mikeb609 says:

    I like Charles Darwin as much as anyone else, but this statement is a bit of a myth:

    “(And Charles Darwin, as Rutherford points out, was the first individual of our species who had that brilliant insight.)”

    Charles Darwin, like all innovators, “stood on the shoulders of giants.” Evolution, even natural selection, had been bandied about for quite some time before Darwin managed to publish his masterful formulation of the theory. Even Darwin’s grandfather, Erasmus, held “transmutationist” ideas.

    And then there’s Alfred Russel Wallace: Same theory, same time, different man.

    http://wallacefund.info/

  2. Jeff Walther says:

    Back in the middle of the 20th century there were volumes called Ace Doubles. They were published by Ace Publishing, and they were two novels in one volume. Each novel was upside down with respect to the other, so that they could both have a front cover. No matter which way you turned the volume, you were looking at the front.

    Anyway, not very important, but a bit of historical trivia about the publishing format of this book.

  3. Clyde Davies says:

    Where should the line be drawn? How about the Russian bio warfare research that set out to develop an even more lethal form of Legionnaire’s Disease?
    http://www.guardian.co.uk/commentisfree/andrewbrown/2012/sep/26/evil-science-soviet-bioweapons-research?INTCMP=SRCH

    Examples like this one should help us to get a less hysterical perspective on current biotech research, especially in crop science

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