Bill Bryson - A short history of nearly everything

We are also uncannily alike. Compare your genes with any other human being’s and on average they will be about 99.9 percent the same. That is what makes us a species. The tiny differences in that remaining 0.1 percent-“roughly one nucleotide base in every thousand,” to quote the British geneticist and recent Nobel laureate John Sulston-are what endow us with our individuality. Much has been made in recent years of the unraveling of the human genome. In fact, there is no such thing as “the” human genome. Every human genome is different. Otherwise we would all be identical. It is the endless recombinations of our genomes-each nearly identical, but not quite-that make us what we are, both as individuals and as a species.

But what exactly is this thing we call the genome? And what, come to that, are genes? Well, start with a cell again. Inside the cell is a nucleus, and inside each nucleus are the chromosomes-forty-six little bundles of complexity, of which twenty-three come from your mother and twenty-three from your father. With a very few exceptions, every cell in your body-99.999 percent of them, say-carries the same complement of chromosomes. (The exceptions are red blood cells, some immune system cells, and egg and sperm cells, which for various organizational reasons don’t carry the full genetic package.) Chromosomes constitute the complete set of instructions necessary to make and maintain you and are made of long strands of the little wonder chemical called deoxyribonucleic acid or DNA-“the most extraordinary molecule on Earth,” as it has been called.

DNA exists for just one reason-to create more DNA-and you have a lot of it inside you: about six feet of it squeezed into almost every cell. Each length of DNA comprises some 3.2 billion letters of coding, enough to provide 10 3,480,000,000possible combinations, “guaranteed to be unique against all conceivable odds,” in the words of Christian de Duve. That’s a lot of possibility-a one followed by more than three billion zeroes. “It would take more than five thousand average-size books just to print that figure,” notes de Duve. Look at yourself in the mirror and reflect upon the fact that you are beholding ten thousand trillion cells, and that almost every one of them holds two yards of densely compacted DNA, and you begin to appreciate just how much of this stuff you carry around with you. If all your DNA were woven into a single fine strand, there would be enough of it to stretch from the Earth to the Moon and back not once or twice but again and again. Altogether, according to one calculation, you may have as much as twenty million kilometers of DNA bundled up inside you.

Your body, in short, loves to make DNA and without it you couldn’t live. Yet DNA is not itself alive. No molecule is, but DNA is, as it were, especially unalive. It is “among the most nonreactive, chemically inert molecules in the living world,” in the words of the geneticist Richard Lewontin. That is why it can be recovered from patches of long-dried blood or semen in murder investigations and coaxed from the bones of ancient Neandertals. It also explains why it took scientists so long to work out how a substance so mystifyingly low key-so, in a word, lifeless-could be at the very heart of life itself.

As a known entity, DNA has been around longer than you might think. It was discovered as far back as 1869 by Johann Friedrich Miescher, a Swiss scientist working at the University of Tübingen in Germany. While delving microscopically through the pus in surgical bandages, Miescher found a substance he didn’t recognize and called it nuclein (because it resided in the nuclei of cells). At the time, Miescher did little more than note its existence, but nuclein clearly remained on his mind, for twenty-three years later in a letter to his uncle he raised the possibility that such molecules could be the agents behind heredity. This was an extraordinary insight, but one so far in advance of the day’s scientific requirements that it attracted no attention at all.

For most of the next half century the common assumption was that the material-now called deoxyribonucleic acid, or DNA-had at most a subsidiary role in matters of heredity. It was too simple. It had just four basic components, called nucleotides, which was like having an alphabet of just four letters. How could you possibly write the story of life with such a rudimentary alphabet? (The answer is that you do it in much the way that you create complex messages with the simple dots and dashes of Morse code-by combining them.) DNA didn’t do anything at all, as far as anyone could tell. It just sat there in the nucleus, possibly binding the chromosome in some way or adding a splash of acidity on command or fulfilling some other trivial task that no one had yet thought of. The necessary complexity, it was thought, had to exist in proteins in the nucleus.

There were, however, two problems with dismissing DNA. First, there was so much of it: two yards in nearly every nucleus, so clearly the cells esteemed it in some important way. On top of this, it kept turning up, like the suspect in a murder mystery, in experiments. In two studies in particular, one involving the Pneumonococcus bacterium and another involving bacteriophages (viruses that infect bacteria), DNA betrayed an importance that could only be explained if its role were more central than prevailing thought allowed. The evidence suggested that DNA was somehow involved in the making of proteins, a process vital to life, yet it was also clear that proteins were being made outside the nucleus, well away from the DNA that was supposedly directing their assembly.

No one could understand how DNA could possibly be getting messages to the proteins. The answer, we now know, was RNA, or ribonucleic acid, which acts as an interpreter between the two. It is a notable oddity of biology that DNA and proteins don’t speak the same language. For almost four billion years they have been the living world’s great double act, and yet they answer to mutually incompatible codes, as if one spoke Spanish and the other Hindi. To communicate they need a mediator in the form of RNA. Working with a kind of chemical clerk called a ribosome, RNA translates information from a cell’s DNA into terms proteins can understand and act upon.

However, by the early 1900s, where we resume our story, we were still a very long way from understanding that, or indeed almost anything else to do with the confused business of heredity.

Clearly there was a need for some inspired and clever experimentation, and happily the age produced a young person with the diligence and aptitude to undertake it. His name was Thomas Hunt Morgan, and in 1904, just four years after the timely rediscovery of Mendel’s experiments with pea plants and still almost a decade before gene would even become a word, he began to do remarkably dedicated things with chromosomes.

Chromosomes had been discovered by chance in 1888 and were so called because they readily absorbed dye and thus were easy to see under the microscope. By the turn of the twentieth century it was strongly suspected that they were involved in the passing on of traits, but no one knew how, or even really whether, they did this.

Morgan chose as his subject of study a tiny, delicate fly formally called Drosophila melanogaster , but more commonly known as the fruit fly (or vinegar fly, banana fly, or garbage fly). Drosophila is familiar to most of us as that frail, colorless insect that seems to have a compulsive urge to drown in our drinks. As laboratory specimens fruit flies had certain very attractive advantages: they cost almost nothing to house and feed, could be bred by the millions in milk bottles, went from egg to productive parenthood in ten days or less, and had just four chromosomes, which kept things conveniently simple.