by Bill Bryson
It is largely because of these complicating factors that cracking the human genome came to be seen almost at once as only a beginning. The genome, as Eric Lander of MIT has put it, is like a parts list for the human body: it tells us what we are made of, but says nothing about how we work. What’s needed now is the operating manual—instructions for how to make it go. We are not close to that point yet.
So now the quest is to crack the human proteome—a concept so novel that the term proteome didn’t even exist a decade ago. The proteome is the library of information that creates proteins. “Unfortunately,” observed Scientific American in the spring of 2002, “the proteome is much more complicated than the genome.”
That’s putting it mildly. Proteins, you will remember, are the workhorses of all living systems; as many as a hundred million of them may be busy in any cell at any moment. That’s a lot of activity to try to figure out. Worse, proteins’ behaviour and functions are based not simply on their chemistry, as with genes, but also on their shapes. To function, a protein not only must have the necessary chemical components, properly assembled, but then must also be folded into an extremely specific shape. “Folding” is the term that’s used, but it’s a misleading one as it suggests a geometrical tidiness that doesn’t in fact apply. Proteins loop and coil and crinkle into shapes that are at once extravagant and complex. They are more like furiously mangled coat hangers than folded towels.
Moreover, proteins are (if I may be permitted to use a handy archaism) the swingers of the biological world. Depending on mood and metabolic circumstance, they will allow themselves to be phosphorylated, glycosylated, acetylated, ubiquitinated, farneysylated, sulphated and linked to glycophosphatidylinositol anchors, among rather a lot else. Often it takes relatively little to get them going, it appears. Drink a glass of wine, as Scientific American notes, and you materially alter the number and types of proteins at large in your system. This is pleasant for drinkers, but not nearly so helpful for geneticists who are trying to understand what is going on.
It can all begin to seem impossibly complicated, and in some ways it is impossibly complicated. But there is also an underlying simplicity in all this, too, owing to an equally elemental underlying unity in the way life works. All the tiny, deft chemical processes that animate cells—the co-operative efforts of nucleotides, the transcription of DNA into RNA—evolved just once and have stayed pretty well fixed ever since across the whole of nature. As the late French geneticist Jacques Monod put it, only half in jest: “Anything that is true of E. coli must be true of elephants, except more so.”
The complex “folded” structure of a protein can clearly be seen in this computer-generated artwork of a protein found in the foot and mouth disease virus. (Credit 26.14)
Every living thing is an elaboration on a single original plan. As humans we are mere increments—each of us a musty archive of adjustments, adaptations, modifications and providential tinkerings stretching back 3.8 billion years. Remarkably, we are even quite closely related to fruit and vegetables. About half the chemical functions that take place in a banana are fundamentally the same as the chemical functions that take place in you.
It cannot be said too often: all life is one. That is, and I suspect will for ever prove to be, the most profound true statement there is.
1 In 1968, Harvard University Press cancelled publication of The Double Helix after Crick and Wilkins complained about its characterizations, which Lisa Jardine has described as “gratuitously hurtful.” The descriptions quoted above are as worded after Watson had softened his comments.
2 Junk DNA does have a use. It is the portion employed in DNA fingerprinting. Its practicality for this purpose was discovered accidentally by Alec Jeffreys, a scientist at the University of Leicester. In 1986 Jeffreys was studying DNA sequences for genetic markers associated with heritable diseases when he was approached by the police and asked if he could help connect a suspect to two murders. He realized his technique ought to work perfectly for solving criminal cases—and so it proved. A young baker with the improbable name of Colin Pitchfork was sentenced to two life terms in prison for the murders.
Field, a sculptural installation by the British artist Antony Gormley. (credit p6.1)
ICE TIME
I had a dream, which was not all a dream.
The bright sun was extinguish’d, and the stars
Did wander … BYRON, “DARKNESS”
In 1815, on the island of Sumbawa in Indonesia, a handsome and long quiescent mountain named Tambora exploded spectacularly, killing a hundred thousand people with its blast and associated tsunamis. No-one living now has ever seen such fury. Tambora was far bigger than anything any living human has experienced. It was the biggest volcanic explosion in ten thousand years—150 times the size of Mount St. Helens, equivalent to sixty thousand Hiroshima-sized atom bombs.
News didn’t travel terribly fast in those days. In London, The Times ran a small story—actually a letter from a merchant—seven months after the event. But by this time Tambora’s effects were already being felt. Two hundred and forty cubic kilometres of smoky ash, dust and grit had diffused through the atmosphere, obscuring the Sun’s rays and causing the Earth to cool. Sunsets were unusually but blearily colourful, an effect memorably captured by the artist J.M.W. Turner, who could not have been happier, but mostly the world existed under an oppressive, dusky pall. It was this deathly dimness that inspired Byron to write the lines quoted above.
Spring never came and summer never warmed: 1816 became known as the year without summer. Crops everywhere failed to grow. In Ireland a famine and associated typhoid epidemic killed sixty-five thousand people. In New England, the year became popularly known as Eighteen Hundred and Froze to Death. Morning frosts continued until June and almost no planted seed would grow. Short of fodder, livestock died or had to be prematurely slaughtered. In every way it was a dreadful year—almost certainly the worst for farmers in modern times. Yet globally the temperature fell by less than 1 degree Celsius. The Earth’s natural thermostat, as scientists would learn, is an exceedingly delicate instrument.
The nineteenth century was already a chilly time. For two hundred years Europe and North America had been experiencing a Little Ice Age, as it has become known, which permitted all kinds of wintry events—frost fairs on the Thames, ice-skating races along Dutch canals—that are mostly impossible now. It was a period, in other words, when frigidity was much on people’s minds. So we may perhaps excuse nineteenth-century geologists for being slow to realize that the world they lived in was in fact balmy compared with former epochs, and that much of the land around them had been shaped by crushing glaciers and cold that would wreck even a frost fair.
A winter fair on a frozen River Thames in London in 1685—a common event during the period known as the Little Ice Age, which lasted until the nineteenth century. (Credit 27.1)
They knew there was something odd about the past. The European landscape was littered with inexplicable anomalies—the bones of Arctic reindeer in the warm south of France, huge rocks stranded in improbable places—and they often came up with inventive but not terribly plausible explanations. One French naturalist named de Luc, trying to explain how granite boulders had come to rest high up on the limestone flanks of the Jura Mountains, suggested that perhaps they had been shot there by compressed air in caverns, like corks out of a popgun. The term for a displaced boulder is an erratic, but in the nineteenth century the expression seemed to apply more often to the theories than to the rocks.
The great British geologist Arthur Hallam has suggested that if James Hutton, the eighteenth-century father of geology, had visited Switzerland, he would have seen at once the significance of the carved valleys, the polished striations, the telltale strand lines where rocks had been dumped, and the other abundant clues that point to passing ice sheets.
Unfortunately, Hutton was not a traveller. But even with nothing better at his disposal than secondhand accounts, Hutton rejected out of han
d the idea that huge boulders had been carried 1,000 metres up mountainsides by floods—all the water in the world won’t make a boulder float, he pointed out—and became one of the first to argue for widespread glaciation. Unfortunately his ideas escaped notice, and for another half-century most naturalists continued to insist that the gouges on rocks could be attributed to passing carts or even the scrape of hobnailed boots.
A boulder sits where it fell out of a melting glacier during the last ice age. Until the nineteenth century, geologists were at a loss to explain how such anomalous rocks, known as erratics, came to be where they are. (Credit 27.2)
Local peasants, uncontaminated by scientific orthodoxy, knew better, however. The naturalist Jean de Charpentier told the story of how in 1834 he was walking along a country lane with a Swiss woodcutter when they got to talking about the rocks along the roadside. The woodcutter matter-of-factly told him that the boulders had come from the Grimsel, a zone of granite some distance away. “When I asked him how he thought that these stones had reached their location, he answered without hesitation: ‘The Grimsel glacier transported them on both sides of the valley, because that glacier extended in the past as far as the town of Bern.’”
Charpentier was delighted, for he had come to such a view himself; but when he raised the notion at scientific gatherings, it was dismissed. One of Charpentier’s closest friends was another Swiss naturalist, Louis Agassiz, who after some initial scepticism came to embrace, and eventually all but appropriate, the theory.
Agassiz had studied under Cuvier in Paris and now held the post of Professor of Natural History at the College of Neuchâtel in Switzerland. Another friend of Agassiz’s, a botanist named Karl Schimper, was actually the first to coin the term “ice age” (in German, Eiszeit), in 1837, and to propose that there was good evidence to show that ice had once lain heavily not just across the Swiss Alps, but over much of Europe, Asia and North America. It was a radical notion. He lent Agassiz his notes—then came very much to regret it as Agassiz increasingly got the credit for what Schimper felt, with some legitimacy, was his theory. Charpentier likewise ended up a bitter enemy of his old friend. Alexander von Humboldt, yet another friend, may have had Agassiz at least partly in mind when he observed that there are three stages in scientific discovery: first, people deny that it is true; then they deny that it is important; finally they credit the wrong person.
At all events, Agassiz made the field his own. In his quest to understand the dynamics of glaciation, he went everywhere—deep into dangerous crevasses and up to the summits of the craggiest Alpine peaks, often apparently unaware that he and his team were the first to climb them. Nearly everywhere Agassiz encountered an unyielding reluctance to accept his theories. Humboldt urged him to return to his area of real expertise, fossil fish, and give up this mad obsession with ice, but Agassiz was a man possessed by an idea.
Louis Agassiz, the Swiss naturalist who became the most outspoken advocate of the idea that much of Earth had once been covered in ice, but alienated many in the process. (Credit 27.3)
Agassiz’s theory found even less support in Britain, where most naturalists had never seen a glacier and often couldn’t grasp the crushing forces that ice in bulk exerts. “Could scratches and polish just be due to ice?” asked Roderick Murchison in a mocking tone at one meeting, evidently imagining the rocks as covered in a kind of light and glassy rime. To his dying day, he expressed the frankest incredulity at those “ice-mad” geologists who believed that glaciers could account for so much. William Hopkins, a Cambridge professor and leading member of the Geological Society, endorsed this view, arguing that the notion that ice could transport boulders presented “such obvious mechanical absurdities” as to make it unworthy of the society’s attention.
Undaunted, Agassiz travelled tirelessly to promote his theory. In 1840 he read a paper to a meeting of the British Association for the Advancement of Science in Glasgow, at which he was openly criticized by the great Charles Lyell. The following year the Geological Society of Edinburgh passed a resolution conceding that there might be some general merit in the theory but that certainly none of it applied to Scotland.
Lyell did eventually come round. His moment of epiphany came when he realized that a moraine, or line of rocks, near his family estate in Scotland, which he had passed hundreds of times, could be understood only if one accepted that a glacier had dropped them there. But, having become converted, Lyell then lost his nerve and backed off public support of the ice age idea. It was a frustrating time for Agassiz. His marriage was breaking up, Schimper was hotly accusing him of the theft of his ideas, Charpentier wouldn’t speak to him and the greatest living geologist offered support of only the most tepid and vacillating kind.
In 1846 Agassiz travelled to America to give a series of lectures, and there at last found the esteem he craved. Harvard gave him a professorship and built him a first-rate museum, the Museum of Comparative Zoology Doubtless it helped that he had settled in New England, where the long winters encouraged a certain sympathy for the idea of interminable periods of cold. It also helped that six years after his arrival the first scientific expedition to Greenland reported that nearly the whole of that semi-continent was covered in an ice sheet just like the ancient one imagined in Agassiz’s theory. At long last, his ideas began to find a real following. The one central defect of Agassiz’s theory was that his ice ages had no cause. But assistance was about to come from an unlikely quarter.
Ladies of an adventurous nature are assisted by guides across a Swiss ice field in 1886. A fashion for Alpine holidays in the late nineteenth century did much to help northern European geologists appreciate the powerful forces of ice. (Credit 27.4)
In the 1860s, journals and other learned publications in Britain began to receive papers on hydrostatics, electricity and other scientific subjects from a James Croll of Anderson’s University in Glasgow. One of the papers, on how variations in the Earth’s orbit might have precipitated ice ages, was published in the Philosophical Magazine in 1864 and was recognized at once as a work of the highest standard. So there was some surprise, and perhaps just a touch of embarrassment, when it turned out that Croll was not an academic at the university, but a janitor.
James Croll, the Scottish janitor and self-taught polymath whose theories concerning Earth’s orbit provided the first plausible explanation for how ice ages might have started. (Credit 27.5)
Born in 1821, Croll grew up poor and his formal education lasted only to the age of thirteen. He worked at a variety of jobs—as a carpenter, insurance salesman, keeper of a temperance hotel—before taking a position as a janitor at Anderson’s (now the University of Strathclyde) in Glasgow. By somehow inducing his brother to do much of his work, he was able to pass many quiet evenings in the university library teaching himself physics, mechanics, astronomy, hydrostatics and the other fashionable sciences of the day, and gradually began to produce a string of papers, with a particular emphasis on the motions of the Earth and their effect on climate.
Croll was the first to suggest that cyclical changes in the shape of the Earth’s orbit, from elliptical (which is to say, slightly oval) to nearly circular to elliptical again, might explain the onset and retreat of ice ages. No-one had ever thought before to consider an astronomical explanation for variations in the Earth’s weather. Thanks almost entirely to Croll’s persuasive theory, people in Britain began to become more responsive to the notion that at some former time parts of the Earth had been in the grip of ice. When his ingenuity and aptitude were recognized, Croll was given a job at the Geological Survey of Scotland and widely honoured: he was made a fellow of the Royal Society in London and of the New York Academy of Science, and given an honorary degree from the University of St. Andrews, among much else.
Unfortunately, just as Agassiz’s theory was at last beginning to find converts in Europe, he was busy taking it into ever more exotic territory in America. He began to find evidence for glaciers practically everywhere he looked, includi
ng near the equator. Eventually he became convinced that ice had once covered the whole Earth, extinguishing all life, which God had then recreated. None of the evidence Agassiz cited supported such a view. Nonetheless, in his adopted country his stature grew and grew until he was regarded as only slightly below a deity. When he died in 1873 Harvard felt it necessary to appoint three professors to take his place.
Yet, as sometimes happens, his theories fell swiftly out of fashion. Less than a decade after his death his successor in the chair of geology at Harvard wrote that the “so-called glacial epoch … so popular a few years ago among glacial geologists may now be rejected without hesitation.”
Part of the problem was that Croll’s computations suggested that the most recent ice age occurred eighty thousand years ago, whereas the geological evidence increasingly indicated that the Earth had undergone some sort of dramatic perturbation much more recently than that. Without a plausible explanation for what might have provoked an ice age, the whole theory fell into abeyance. There it might have remained for some time had it not been for a Serbian academic named Milutin Milankovitch, who had no background in celestial motions at all—he was a mechanical engineer by training—but who in the early 1900s developed an unexpected interest in the matter. Milankovitch realized that the problem with Croll’s theory was not that it was incorrect but that it was too simple.
Milutin Milankovitch, a Serbian mechanical engineer and mathematician who refined and broadened Croll’s theories while a prisoner of war in Budapest. (Credit 27.6)
