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Authors: Adam Rutherford

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Like many of the invented techniques in this chapter, this is a proof of principle. As a means of information storage, DNA's resilience is irrefutable. George Church and others have taken the simple fact that DNA can carry a code and have rewritten it to store nonbiological data. The stability of DNA and the falling costs of the technology used give this technique potential for archiving data at a breathtaking density: the authors claim 5.5 petabits per cubic millimeter (i.e., one quadrillion units of information). This is a more concentrated from of data storage than a Blu-ray Disc, a flash drive, or even the hard drive on your computer. What has been achieved so far is only useful for archiving, as the technology to write and access the memory stored in DNA takes many days; electrical circuitry in a computer can save an equivalent amount of data in seconds. Yet it is not inconceivable that one day computers might store their memories not in silicon chips, but in DNA chips.

That creative engineering philosophy is key to synthetic biology: how can we redesign and use biological technology for purpose? All of the endeavors described above are nascent technologies, still very much in the experimental phase. Yet they all demonstrate that the limits of nature are being surpassed by our own inventions. We have always adapted nature for our benefit, and in the era of molecular biology we have done so by remixing it at a molecular level. Now, for the first time, we are engineering living systems created in ways that rewrite the very language evolution has provided.

Acknowledgments

Just like science, writing this book has been a collaborative process. I wrote the words, but
Creation
is a concatenation and remix assembled from the ideas and work of others. My thinking on the subject of the origin of life is heavily influenced by my friend Nick Lane at University College London. I embarked on
Creation
before reading his outstanding book
Life Ascending
. But, having done so now, and for our many lunches, I am profoundly indebted to him. In the first half, I've liberally borrowed from his thoughts, which he expresses with virtuoso clarity. I urge you to read it.

Many of the interviews and much of the research for this book were drawn from my involvement in BBC radio and television productions. In 2009, I presented a documentary series on BBC4 called
The Cell
, which during the course of three hours covered the story of biology from van Leuwenhoek to synthetic biology. This was made by a team of brilliant filmmakers including Jacqui Smith, Andrew Thompson, Alison Rooper, Nick Jordan, and Jill Fullerton Smith. Particularly, David Briggs did significant research on the seventeenth-, eighteenth-, and nineteenth-century microscopists, and deserves acres of credit for academically and meticulously collating multiple original sources. In 2010, we followed this up with a BBC Radio 4
Frontiers
program on the current status of origin-of-life biology. Roland Pease produced and immense gratitude is due to him as well as to Sasha Feachem and Deborah Cohen at the BBC Radio Science Unit. During the writing of
Creation
, I presented an episode of the long-running BBC flagship science program
Horizon
on synthetic biology. Matthew Dyas, Kelly Neaves, and Aidan Laverty skilfully guided that into the world. Some of the interviews quoted in
Creation
were conducted under the auspices of those programs.

Here are some others to whom I owe a debt of gratitude: Jane Sowden, my friend and PhD supervisor, from whom I learned how to be a good scientist; Steve Jones, for teaching me, inspiring me, and appearing as a contributor in almost all of my television and radio programs; Armand Leroi, for helping me with Aristotle by showing me chapters from his forthcoming book
Aristotle's Lagoon
; Matt Ridley, for providing scientific and biographical information on Francis Crick; Rob Carlson, author of the excellent book
Biology is Technology
, for his help on many aspects of synthetic biology; Alex Taylor and Vitor Pinheiro, for much-needed guidance on XNA and expanded genetic code; John Sutherland, for RNA synthesis; Zita Martins, for her expertise on astrobiology and Martian rocks; Emma Perry, for helping me with the school curriculum; Sinjoro Simon Varwell, dankon; those on Twitter who have at times responded to my pleas to find the right word, fungus, or reptile, specifically @Mr._muse, @sarcasmaniac, @janieface1, @writerJames; Kirby Ferguson, for copyright and remixing; Richard Kelwick, for the UK iGEM meet up; Philip Campbell, Kerri Smith, Charlotte Stoddart, Geoff Marsh, and Thea Cunningham, and all my friends at
Nature
.

I was nomadic in writing, though rarely ventured out of Hackney, London. The following kind people allowed me to use their various spaces: Jack and Lynsey Mathew—and Barney for keeping me company (Lynsey also for the word “jumentous”); John Sanders and Beth Gibbon; Ana-Paula Lloyd and Jonny Hassid; and everyone at my second home, Mouse and De Lotz—quite clearly the best café in London.

Several people read and commented on the manuscript during its lengthy gestation. However, any errors or mutations that have survived these rounds of selection are mine alone. I wish to thank Ed Yong, Jim Al-Khalili, Matt Ridley, Dara Ó Briain, Matthew Cobb, Brian Cox, Suzi Gage, David Adam, Nathaniel Rutherford, and David Watson for their advice, conversation, and edits; and particularly Kevin Fong, with whom I have shared the chronic condition of writing. I tested many of the ideas in this book on him.

I am tremendously grateful to my agents, Sophie Laurimore and Will Francis; without Will's continual support
Creation
could never have happened; my wife Georgia and my children, who have supported its genesis unflinchingly; my love for them is as deep as geological time. Most of all, I humbly thank my editors at Penguin, Brooke Carey, Katie Coe, and Will Hammond, who wrestled with me and these words countless times to batter them into shape. I doubt many writers receive as much attention in sculpting their prose.

Scientists can be a quarrelsome lot. They compete for ideas and for funding and, just like in any human endeavor, are subject to dogma and whimsy and hard-felt beliefs. Good theories emerge from that maelstrom of open—but sometimes fractious—debate, and get tested and refined by experiment. Science does not settle on truth, but tends toward it. These particular areas of science are pioneering and important and, as such, they are subject to quarrel perhaps more than most. The ideas presented here will be refined or changed over time, or rejected. And frankly, like all good scientists should, I look forward to being corrected.

Annotated Bibliography

We luxuriate in a time where the basic mechanisms of life on Earth are largely understood, and many great books have been written that describe evolution and genetics. My recent favorites include
Life Ascending
by Nick Lane (Profile Books, 2010),
Why Evolution Is True
by Jerry A. Coyne (Oxford University Press, 2010),
Your Inner Fish
by Neil Shubin (Penguin Books Limited, 2009), and almost everything by Steve Jones, particularly
The Language of the Genes
(HarperCollins, 1993; despite its being written twenty years ago, ten years before the Human Genome Project was first published, it contains insight and stories as good as any contemporary book on the nature of DNA), and
Almost Like a Whale
(Black Swan, 2000), which successfully updates the
Origin of Species
with contemporary evolutionary biology. Of course, reading anything by Charles Darwin will make you smarter. His works are as important to our culture as anything by any writer.

A Note on Latin, Plurals, and Language

Bacteria have existed longer and in greater number than any other group of organisms. Though invisible to the naked eye their total biomass exceeds that of both animals and plants. All other life on Earth is dependent on bacteria, including our own, as we carry trillions of these cells on and in our bodies.

Bacteria are also cornerstones of the era of molecular biology revolution, providing both the tools of genetic manipulation (restriction enzymes) and the medium in which almost all genetic engineering takes place.

In this book I have used the word
bacteria
to mean both single and multiple cells, rather than bacterium for a single cell. This is on the principle that its adoption into the ever-evolving English language releases it through usage from the grammatical rules of its neo-Latinate origin.

Part I: The Origin of Life

Chapter 1: Begotten, Not Created

As with all science, the pathways to great discoveries are complex, tortuous, and winding, and almost always bereft of eureka moments. The road that led from Van Leeuwenhoek to cell theory is no different, with dozens of people making small incremental experimental and conceptual advances. I have outlined the narrative of just some of the key players. For a thorough and scholarly history of the early microscopists, Professor Sir Henry Harris's
The Birth of the Cell
(Yale University Press, 2000) is the definitive guide, from which I have sourced many sections in the story of cell theory.

Animalia
(
The History of Animals
) by Aristotle, 350
BCE
, translated by D'Arcy Wentworth Thompson in 1910, is thoroughly readable and well worth a look. It is available for free online at http://classics.mit.edu/Aristotle/history_anim.html.

Chapter 2: Into One

Plenty has been written about Gregor Mendel, as befits one of the great scientists, and here is the original paper where he outlines what would become the laws of inheritance: G. Mendel, “Versuche über Pflanzen-hybriden,”
Verhandlungen des Naturforschenden Vereines
4, Abh. Brünn (1866), pp. 3–47, or in translation: “Experiments in Plant Hybridization,”
Journal of the Royal Horticultural Society
26 (1901), pp. 1–32.

That there were 115 copies of that paper, none of which made it into Darwin's library, is documented here: R. C. Olby, “Mendels Vorlaüfer: Kölreuter, Wichura, und Gärtner,”
Folia Mendeliana
21 (1986), pp. 49–67.

One point of Mendelian interest lies in reanalysis of his data by Ronald Fisher, one of the founders of modern evolutionary biology (along with J. B. S. Haldane, whom I'm told he could not stand to be in the same room with, and Sewall Wright). Fisher concluded that the statistical significance of Mendel's results meant the experiments must have been “falsified so as to agree closely with Mendel's expectations.” He wasn't alleging that the laws are incorrect, merely that the results were precise enough to suggest massaging. This has been repeated often since, but the following paper by the geneticists Daniel Hartl and Daniel Fairbanks concludes that this allegation can be put down “because on closer analysis it has proved to be unsupported by convincing evidence”: Daniel L. Hartl and Daniel J. Fairbanks, “Mud Sticks: On the Alleged Falsification of Mendel's Data,”
Genetics
175:3 (March 2007), pp. 975–79.

The story of twentieth-century biology and, indeed, science, orbits around probably the most significant scientific advance of that century—Crick and Watson's publication of the double helix. For more on the story of DNA, there are plenty of books available. James Watson's own account,
The Double Helix
, is a gripping read (reissued by Simon & Schuster, 2012), though is very clearly a personal account by a fabulous storyteller, and to my mind bears the signature of mythmaking. His treatment of Rosalind Franklin in that book is horrid. Franklin's role in the story of DNA is frequently debated, often with the question, should she have gotten the Nobel Prize alongside Crick and Watson? There is a simple and absolute answer to that, which is no: the rules are that Nobel Prizes will not be given posthumously, and Franklin was prematurely dead by the time DNA was recognized by the awarding committee in 1962. Brenda Maddox's biography
Rosalind Franklin: The Dark Lady of DNA
(HarperCollins, 2003) is thrilling, comprehensive, and honest, portraying Franklin in a believable and not always flattering light. It is a marvelous book.

Francis Crick, as befits his genius, appears in several different sections of this book, as he continued to explore the nature of life after his and Watson's grand discovery in 1953. There isn't a better description of his life and works than Matt Ridley's
Francis Crick: Discoverer of the Genetic Code
(HarperCollins, 2011).

The BBC dramatization of the tale of DNA is entitled
Life Story
(known in the United States as
The Race for the Double Helix
or
Double Helix
) (1987), and is thoroughly watchable. It features Hollywood's favorite otherworldly quirky scientist actor, Jeff Goldblum, in the role of otherworldly quirky scientist Jim Watson. As an aside, Goldblum has also played a neurosurgeon (
The Adventures of Buckaroo Banzai Across the 8th Dimension
, 1984), a particle physicist (
The Fly
, 1986), a mathematician (
Jurassic Park
, 1993), a computer scientist and environmentalist (
Independence Day
, 1996), a canine immunologist (
Cats & Dogs
, 2001), and a marine biologist (
The Life Aquatic with Steve Zissou
, 2004). Can any other actor boast such a litany of scientists?

“We wish to suggest a structure for the salt of deoxyribonucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest.” So begins probably the most famous and significant research paper of the twentieth century: J. D. Watson and F. H. C. Crick, “A Structure for Deoxyribose Nucleic Acid,”
Nature
171 (April 25, 1953), pp. 737–38. This is available at www.nature.com/nature/dna50/archive.html, along with several other landmark papers by titans of biology from this golden age, including O. T. Avery, C. M. MacLeod, and M. McCarty, “Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types,”
Journal of Experimental Medicine
79 (1944), pp. 137–59.

Language is the most useful and frequently used metaphor for understanding and explaining the workings of DNA. Language also shares many similar evolutionary characteristics, as explained in this review by biologist Mark Pagel: “Human Language as a Culturally Transmitted Replicator,”
Nature Reviews Genetics
10 (2009), pp. 405–15 (doi:10.1038/nrg2560). For a terrifically enjoyable nonscientific romp though the evolution of words and language, read Guy Deutcher's
The Unfolding of Language: An Evolutionary Tour of Mankind`s Greatest Invention
(Arrow, 2006).

For Douglas Theobald's statistical analysis of Luca's existence, see his “A Formal Test of the Theory of Universal Common Ancestry,”
Nature
465 (May 13, 2010), pp. 219–22 (doi:10.1038/nature09014); and a rebuttal: Takahiro Yonezawa and Masami Hasegawa, “Was the Universal Common Ancestry Proved?”
Nature
468, E9 (December 16, 2010), pp. 219–22 (doi:10.1038/nature09482).

This paper describes a model that explores the idea that a preponderance of the bases CG might indicate a proximity to hot vents: Laurence D. Hurst and Alexa R. Merchant, “High Guanine-cytosine Content Is Not an Adaptation to High Temperature: A Comparative Analysis Among Prokaryotes,”
Proceedings of the Royal Society B
268 (2001), pp. 493–7 (doi:10.1098/rspb.2000.1397).

On some of the earliest fossils of cells: David Wacey et al
.
, “Microfossils of Sulfur-metabolizing Cells in 3.4-billion-year-old Rocks of Western Australia,”
Nature Geoscience
4 (2011), pp. 698–702 (doi:10.1038/ngeo1238).

There are many papers on bacteria and archaea swapping genes rather than inheriting them from their cellular parents. One of the most graphic is: V. Kunin et al., “The Net of Life: Reconstructing the Microbial Phylogenetic Network,”
Genome Research
15 (2005), pp. 954–59, which features a necessarily baffling diagram of the tangled bank of the base of the tree of life.
New Scientist
, a magazine with a proud history, decided to focus its attention on this precise subject on the bicentennial of Darwin's birth in 2009. The bold cover title was “Darwin Was Wrong,” though the articles inside were more nuanced about the subject of lateral or horizontal gene transfer. They explained in an accompanying editorial:

As we celebrate the 200th anniversary of Darwin's birth, we await a third revolution that will see biology changed and strengthened. None of this should give succor to creationists, whose blinkered universe is doubtless already buzzing with the news that “
New Scientist
has announced Darwin was wrong.” Expect to find excerpts ripped out of context and presented as evidence that biologists are deserting the theory of evolution en masse. They are not.

On seven separate occasions I was presented with this cover (or someone quoting it) at public meetings as part of attacks from particular religious groups who choose to ignore evidence and assert creationist doctrine.

Chapter 3: Hell on Earth

See Euan Nisbet's classic textbook,
The Young Earth: An Introduction to Archaean Geology
(Allen and Unwin, 1987), on the first couple of billion years of our planet.

This study suggests that comets delivered water to the earth and the moon: James P. Greenwood et al., “Hydrogen Isotope Ratios in Lunar Rocks Indicate Delivery of Cometary Water to the Moon,”
Nature Geoscience
4 (2011), pp. 79–82 (doi:10.1038/ngeo1050).

An interesting model that suggests microbial life could have survived underwater during the intense barrage of the Late Heavy Bombardment can be found in Oleg Abramov and Stephen J. Mojzsis's, “Microbial Habitability of the Hadean Earth During the Late Heavy Bombardment,”
Nature
459 (May 21, 2009), pp. 419–22 (doi:10.1038/nature08015); Lynn J. Rothschild, “Earth Science: Life Battered but Unbowed,”
Nature
459 (May 21, 2009), pp. 335–36 (doi:10.1038/459335a); and Simon A. Wilde et al
.
, “Evidence from Detrital Zircons for the Existence of Continental Crust and Oceans on the Earth 4.4 Gyr Ago,”
Nature
409 (January 11, 2001), pp. 175–78 (doi:10.1038/35051550).

One of the key studies that showed that the moon was blasted off the very young Earth by an impact from another large celestial body, Theia, the Titan of ancient Greek myth who gave birth to the Moon goddess, Selene, is: U. Wiechert et al., “Oxygen Isotopes and the Moon-Forming Giant Impact,”
Science
294 (October 12, 2001), pp. 345–48 (doi:10.1126/science.1063037).

On Darwin's handwriting: as part of the filming of BBC4's
The Cell
, I had the great privilege to hold in my ungloved hands the letter Darwin sent to Joseph Hooker in 1871 in which he ponders his now-famous “warm little pond.” Standing in a reading room in the University of Cambridge Library, I read an extract from this priceless piece of history. After several takes were spoiled because I couldn't decipher his scrawl, we ended up slipping a printed transcript on top of the actual letter. It is, of course, entirely irrelevant that his handwriting was so awful, but I find this quite amusing.

J. B. S. “Jack” Haldane is one of the dominant figures of twentieth-century biology in many of its forms, and a truly fascinating chap. Not only did he ponder the origin and nature of life and species, he was a central figure in the fusion of genetics and evolutionary biology and many other fundamental aspects of the living world, and back in 1923 he was probably the first person to suggest hydrogen as a basis for renewable energy. He was a Marxist and vocally spoke out against the British government's role in the Suez Crisis in 1956. His classic essay “On Being the Right Size” is available for free online, as is a very curious film presented by Haldane (produced by the Soviet Film Agency, 1940) entitled
Experiments in the Revival of Organisms
, which features the posthumous physical reactions of a severed dog's head. Unfortunately, the definitive biography by Ronald Clark,
The Life and Works of J. B. S. Haldane
(1968), is currently out of print.

This is Stanley Miller's iconic experiment from 1953: S. L. Miller, “A Production of Amino Acids under Possible Primitive Earth Conditions,”
Science
117 (May 15, 1953), pp. 528–29 (doi:10.1126/science.117.3046.528).

And Jeffrey Bada's 2008 analysis of some of Miller's experiments: Adam P. Johnson et al., “The Miller Volcanic Spark Discharge Experiment,”
Science
322 (17 October 2008), p. 404 (doi:10.1126/science.1161527).

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