Life's Greatest Secret

‘Matthew Cobb is a respected scientist and historian, and he has combined both disciplines to spectacular effect in this compelling, authoritative and insightful account of how life works at the deepest level. It’s a bloody brilliant book.’
Professor Brian Cox

‘Life’s Greatest Secret
is the logical sequel to Jim Watson’s
The Double Helix.
While Watson and Crick deserve their plaudits for discovering the structure of DNA, that was only part of the story. Beginning to understand how that helix works – how its DNA code is turned into bodies and behaviours – took another fifteen years of amazing work by an army of dedicated men and women. These are the unknown heroes of modern genetics, and their tale is the subject of Cobb’s fascinating book.’
Jerry Coyne,
University of Chicago and author of
Why Evolution is True

‘Most people think the race to sequence the human genome culminated at the 2000 White House “Mission Accomplished” announcement. In
Life’s Greatest Secret,
we learn that it was just one chapter of a far more interesting and continuing story.’
Eric Topol,
Professor of Genomics and Director, Scripps Translational Science Institute and author of
The Patient Will See You Now

‘Gripping, insightful history, often from the mouths of the participants themselves.’
Kirkus Reviews

‘Rich, thrilling and thorough, this is the definitive history of arguably the greatest of all scientific revolutions.’
Adam Rutherford,
science writer, broadbcaster and author of
Creation

‘Writing with flair, charisma and authority, this is Cobb’s magnum opus. But more important than that, this is humankind’s magnum opus. This is the story of a great human endeavour – a global adventure spanning decades – which unravelled how life really works. No area of science is more fundamental or more important; read about it and be filled with wonder.’
Daniel M. Davis,
author of
The Compatibility Gene

‘Cobb reveals the astonishing drama of the moment genetics and information technology collided, shaping the modern world and modern thought.’
Paul Mason,
Channel 4 News

Copyright © 2015 by Matthew Cobb

First published in Great Briain in 2015 by

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10  9  8  7  6  5  4  3  2  1

1

Genes before DNA

2

Information is everywhere

3

The transformation of genes

4

A slow revolution

5

The age of control

6

The double helix

7

Genetic information

8

The central dogma

9

Enzyme cybernetics

10

Enter the outsiders

11

The race

12

Surprises and sequences

13

The central dogma revisited

14

Brave new world

15

Origins and meanings

Conclusion

The RNA genetic code, as finally established in 1967. U, C, A and G are the RNA bases. The 20 naturally occurring amino acids are given in the table, as three-letter abbreviations (e.g. Phe = phenylalanine). In RNA, Uracil (U) replaces the Thymine (T) base found in DNA. AUG codes for both methionine (Met) and for the start of the message. Slight variants of this code are found in some species, and in the mitochondria that are found in our cells – see Chapter 12.

An outline of how the genetic code works during protein synthesis. A DNA double helix in the cell nucleus is partially unravelled and one strand is transcribed into RNA (mRNA). In organisms with a cell nucleus, this mRNA often contains irrelevant sequences (introns) that are spliced out to form mature mRNA which then leaves the nucleus. In the cell’s cytoplasm, RNA-based ribosomes read the message, beginning at AUG. Transfer RNA (tRNA) molecules, synthesised by the cell from its DNA, carry on one side an anti-codon that binds with a particular mRNA codon and, on the other side, a binding site that links to a specific amino acid. In a process known as translation, tRNA molecules attached to an amino acid shuttle through the ribosome, bind with the mRNA codon and release their amino acid, thereby creating a protein chain.

In April 1953, Jim Watson and Francis Crick published a scientific paper in the journal
Nature
in which they described the double helix structure of DNA, the stuff that genes are made of. In a second article that appeared six weeks later, Watson and Crick put forward a hypothesis with regard to the function of the ‘bases’ – the four kinds of molecule that are spaced along each strand of the double helix and which bind the two strands together. They wrote: ‘it therefore seems likely that the precise sequence of the bases is the code which carries the genetical information.’

This phrase, which was almost certainly the work of Crick, must have seemed both utterly strange and completely familiar to those who read the article. It was strange because nothing so precise had ever been said before – no one had previously referred to ‘genetical information’. This was a category that Watson and Crick had just invented. And yet it was familiar because it fitted so well with the ideas that were in the air at the time. It was adopted without debate; this new way of looking at life seemed so obvious that it was immediately accepted by scientists around the world. Today, these words, or something like them, are said every day in classrooms all over the planet as teachers explain the nature of genes and what they contain.

This book explores the surprising origin of these ideas, which can be traced back to physics and mathematics, and to wartime work on anti-aircraft guns and signals communication. It describes the way in which these concepts entered biology through the then-fashionable field of cybernetics, and how they were transformed as biologists sought to understand life’s greatest secret – the nature of the genetic code. It is a story of ideas and experimentation, of ingenuity, insight and dead-ends, and of the race to make the greatest discovery of twentieth-century biology, a discovery that has opened up a brave new world for the twenty-first century.

Manchester, April 2015

–   ONE   –

In the early decades of the nineteenth century, the leaders of the wool industry in the central European state of Moravia were keen to improve the fleeces produced by their sheep. Half a century earlier, a British businessman farmer called Robert Bakewell had used selective breeding to increase the meat yield of his flocks; now the Moravian wool merchants wanted to emulate his success. In 1837 the Sheep Breeders’ Society organised a meeting to discuss how they could produce more wool. One of the speakers was the new Abbot of the monastery at Brnö, a city that was at the heart of the country’s wool production. Abbot Napp was intensely interested in the question of heredity and how it could be used to improve animal breeds, fruit crops and vines; this was not simply a hobby – the monastery was also a major landowner. At the meeting, Napp argued that the best way to increase wool production through breeding would be to address the fundamental underlying issue. As he put it impatiently: ‘What we should have been dealing with is not the theory and process of breeding. But the question should be:
what is inherited and how
?’
¹

This question, which looks so straightforward to us, was at the cutting edge of human knowledge, as the words ‘heredity’ and ‘inheritance’ had only recently taken on biological meanings.
²
Despite the centuries-old practical knowledge of animal breeders, and the popular conviction that ‘like breeds like’, all attempts to work out the reasons behind the various resemblances between parents and offspring had foundered when faced with the range of effects that could be seen in human families: skin colour, eye colour and sex all show different patterns of similarity across the generations. A child’s skin colour tends to be a blend of the parental shades, their eye colour can sometimes be different from both parents, and in all except a handful of cases the sex of the child is the same as only one parent. These mysterious and mutually contradictory patterns – all of which were considered by the seventeenth-century physician William Harvey, one of the first people to think hard about the question – made it impossible to come up with any overall explanation using the tools of the time.
³
Because of these problems it took humanity centuries to realise that something involved in determining the characteristics of an organism was passed from parents to offspring. In the eighteenth and early nineteenth centuries, the tracing of human characteristics such as polydactyly (extra fingers) and Bakewell’s selective breeding had finally convinced thinkers that there was a force at work, which was termed ‘heredity’.
⁴
The problem was now to discover the answer to Napp’s question – what is inherited and how?

Napp had not made this conceptual breakthrough alone: other thinkers such as Christian André and Count Emmerich Festetics had been exploring what Festetics called ‘the genetic laws of nature’. But unlike them, Napp was able to organise and encourage a cohort of bright intellectuals in his monastery to explore the question, a bit like a modern university department focuses on a particular topic. This research programme reached its conclusion in 1865, when Napp’s protégé, a monk named Gregor Mendel, gave two lectures in which he showed that, in pea plants, inheritance was based on factors that were passed down the generations. Mendel’s discovery, which was published in the following year, had little impact and Mendel did no further work on the subject; Napp died shortly afterwards, and Mendel devoted all his time to running the monastery until his death in 1884. The significance of his discovery was not appreciated, and for nearly two decades his work was forgotten.
⁵
But in 1900 three European scientists – Carl Correns, Hugo de Vries and Erich von Tschermak – either repeated Mendel’s experiments or read his paper and publicised his findings.
⁶

The century of genetics had begun.

*

The rediscovery of Mendel’s work led to great excitement, because it complemented and explained some recent observations. In the 1880s, August Weismann and Hugo de Vries had suggested that, in animals, heredity was carried by what Weismann called the germ line – the sex cells, or egg and sperm. Microscopists had used newly discovered stains to reveal the presence of structures inside cells called chromosomes (the word means ‘coloured body’) – Theodor Boveri and Oscar Hertwig had shown that these structures copied themselves before cell division. In 1902, Walter Sutton, a PhD student at Columbia University in New York, published a paper on the grasshopper in which he used his own data and Boveri’s observations to audaciously suggest that the chromosomes ‘may constitute the physical basis of the Mendelian law of heredity’.
⁷
As he put it in a second paper, four months later: ‘we should be able to find an exact correspondence between the behaviour in inheritance of any chromosome and that of the characters associated with it in the organism’.
⁸