Читать книгу Masterminds: Genius, DNA, and the Quest to Rewrite Life - David Duncan Ewing - Страница 7

Science has given us the means to create utopia and dystopia, incinerate and mutate ourselves, build elevators into space, and tinker with the Lego blocks of life. Yet most people blanche when they see terms such as deoxyribonucleic acid—better known as DNA. Stare at your left hand and, if you could see them, you would glimpse billions of deoxyribonucleic acid molecules tucked just inside the cells that make up your hand. The eyes you are using to stare at your pinky contain deoxyribonucleic acid. Your eyes were made according to instructions stored in you in those nucleotides, and they continue to see thanks to eyeball maintenance programs stowed in your DNA.

Try saying deoxyribonucleic acid. It’s not too hard, even if it sounds sciency. Die-ox-ee-ribe-o-nuke-lay-eek acid. DNA is a three-dimensional information-storage molecule—a collection of atoms joined together by chemical bonds—drawn by chemists as a two-dimensional figure on a page that looks like this:

DNA is composed of three materials: first, a microscopic hunk of sugar called a deoxyribose that is joined to a second component, a phosphate, that links the deoxyribose sugars. This sugar-phosphate “ladder” is the superstructure of DNA, its outer backbone supporting the third ingredient, the nucleic acids, also known as bases. These bases are much like the zeros and ones in binary computer code, except that instead of two elements to the code, DNA contains four bases: adenine (A), cytosine (C), guanine (G), and thymine (T). And instead of encoding programs on a computer, the sequence of these bases provides instructions to create and maintain a living organism.

Are your eyes already glazing? Well, think of this as learning to drink wine, which most people don’t like at first but keep trying until it becomes quite a nice sensation. Scientific concepts will not be quite so sweet, or dry, for most nonscientists. Nor will they give you a pleasant buzz. But having at least a rudimentary knowledge of the language and concepts of modern biology could save your life, or your children’s. It could prevent you or others from becoming unduly frightened of new discoveries that are safe or it could make you knowledgeable enough to be frightened of science that is not. If you can use a recipe to bake mustard-lemon halibut, or comprehend the difference between a concerto and a symphony, you can get this stuff. Absorb these ideas as you might the basics of how to write a haiku poem or a rock lyric, or read box scores in the sports section.

You don’t need to know how to say the chemical name for DNA to read this book, but it’s a little like reading a Dickens novel without really learning the names of Oliver Twist, Nicholas Nickleby, and David Copperfield. Granted, mitochondria, enzyme, and polymorphism lack the ring of Twist and Copperfield. They seem to have been decided on by scientists whose imagination did not include concocting snappy names, a misfortune that has hardly helped the cause of enlivening the scientific debate. Scientists, along with lawyers and engineers, have created over the centuries a complicated language that makes it easy for members of their science-speak caste to talk to one another, but sounds like mumbo jumbo to everyone else.

The story begins with a cell—the basic unit of life, the universe where most of the action takes place in the science part of this story. Nearly all life-forms are comprised of cells, either just one or, in the case of humans, about 100 trillion. Many cells contain a central glob called a nucleus filled with chromosomes, twenty-three pairs in humans, and various numbers in other organisms. In most of the living creatures you see (such as ourselves, mice, goats, fish, plants, starfish), these chromosomes contain two complete sets of the genome, one each from the organism’s parents—except sperm and egg cells, which contain only one complete set, and red blood cells, which have no nucleus. (There a few exceptions to this, but they are not important to understanding the concept.) The chromosomes are made out of DNA, which in a human consists of around 3 billion base pairs from each parent, for a total of 6 billion. The DNA is arranged in pairs like the rungs on a ladder, the rungs twisted elegantly into the famous double helix, discovered by Watson and Crick in 1953. If each base pair were the size of a letter on the page of this book, the strand would run from my office in San Francisco to my hometown of Kansas City, Missouri. Writing it all down in a book would take 500,000 pages.

These pairs are arranged in linear sequences of up to several thousand bases called genes—some thirty thousand of them in a human, and a few hundred of them in the simplest single-celled bacterium. (The exact number of human genes is still debated; there also are millions of base pairs that apparently do nothing, so-called junk DNA, though recent findings suggest that more may be going on amid this “junk” than has been previously realized.) The arrangement of the base pairs into sequences of As, Ts, Cs, and Gs is the basic code of life. Remarkably, DNA figured out eons ago how to replicate itself and to be read by the cell to perform functions. (Little is known about how primordial DNA molecules on the ancient Earth figured out how to copy themselves; efforts to piece together a mechanistic picture of how this happened have been ongoing since the 1950s). This is because each nucleotide is designed by evolution to pair with another specific nucleotide. As like to pair with Ts, and Gs with Cs. When DNA replicates it splits in half, with the assistance of certain proteins, with each strand of the double-helix ladder separating like a zipper unzipping. The exposed bases then have the ability to pair with complementary nucleotides. Processes in the cell then help seek out loose nucleotides floating around and chemically incorporate them into the growing DNA chain—As pair with Ts, Gs with Cs, and so forth, voilà, a new set of complete chromosomes.

DNA’s second mission is to carry the code used to create proteins, which are encoded by genes. Proteins are sequences of amino acids; they look something like a linear pearl necklace bunched up into a ball, with each pearl being a different amino acid (there are twenty different types of amino acids generally used in proteins). Even though humans are thought to have only 30,000 genes, our cells make many times that number of different proteins. Proteins are the key structural components of life and also serve as the machines that accelerate chemical reactions (if a protein accelerates a chemical reaction, it is called an enzyme). Proteins turn genes on and off, proteins recognize and eliminate invading infectious organisms, proteins unzip and help copy DNA. In short, life as we know it is largely handled by these elegantly designed protein nano-machines designed over the millennia by evolution.

Proteins wad up into specific three-dimensional shapes that interact with other three-dimensional shapes, including other proteins, the blobs often attracted to each other by chemical and electrical bonds that cause reactions that regulate everything from memory storage in a brain cell to tears in our eyes when we are sad. Each amino acid is coded by a three-base sequence. For instance, the amino acid alanine—abbreviated A—is coded by GCG, and the amino acid histidine—an H—is coded by CAC. So let’s say the gene sequence of my crooked toe starts with GCG, which makes an A, and then CAC, which makes an H. Then repeat GCGCAC six times. The resulting protein would have an amino acid sequence like this: AHAHAHAHAHAH, and on and on, depending on the sequence of the DNA.

Proteins are not made directly from the master code recorded on your DNA. Rather, they are manufactured with the help of an intermediary molecule called RNA that carries nucleotide instructions to direct the assembly of each protein molecule (a single RNA molecule can be used to direct the synthesis of multiple copies of the same protein molecule). Like DNA, RNA is composed of a linear sequence of bases, As, Cs, and Gs, but it has a U for uracil instead of a T. In a process called transcription, special proteins called RNA polymerases sit on top of a region of DNA containing a gene. These RNA polymerases then synthesize an RNA molecule based on the linear sequence of the gene. This special RNA molecule is called messenger RNA, and its sole purpose is to direct the synthesis of proteins based on its sequence. Messenger RNAs are assisted by ribosomes, a tiny protein assembly factory in the cell that is partly made up of RNA and partly made of protein. Its job is to chemically build proteins using the assembly instructions contained on the messenger RNA. Each three-letter base code in the messenger RNA designates a specific amino acid. Loose amino acids in the cell are recruited to the ribosome and chemically linked together into a growing protein chain. (Amino acids come from food we eat.)

Sometimes when genes are replicated, mistakes are made—a letter (base) is missing, or the order of bases is scrambled or duplicated too many times. These errors are mutations, which happen frequently, it seems—though how often is open to debate as certain researchers say the rate of mutation is constant, while others say it goes up and down based on whether or not an organism needs to mutate or not. Most mutations have a neutral effect, though some simple mutations—swapping an A for a G, for example, in a particular gene—can be fatal or helpful, by offering some sort of evolutionary advantage. The idea of mutation is one of the key tenets of Charles Darwin’s theory of natural selection, though he knew nothing about DNA—that mutations and differences in hereditary material from one generation to another account for adaptations that favor some organisms over others. For instance, at some point early humanoids figured out that by standing upright on the savannas of Africa they could see quarry to hunt or a hungry saber-toothed tiger bearing down on them. Those humanoids had a tiny difference in their DNA that allowed them to stand more upright than other humanoids did not get eaten, and therefore survived—along with the genes for uprightness.

Not all genes are found in chromosomes. A few live inside little structures within cells called mitochondria, which billions of years ago were parasites that entered primitive cells and became a crucial part of the cell’s energy-processing machinery. With a circular band of genes separate from an organism’s chromosomes, mitochondria provide most of the power to cells, helping convert food into energy.

Most base pairs—over 99 percent of them—are identical in every human, with only about one in a thousand bases diverging to make us distinct. These differences in the human recipe account for variations in everything from eye color to disease. They account for the differences between James Watson and a supermodel, an Olympic pentathlete with no hair and a math whiz with dreadlocks.

Most differences in humans involve just one set of base pairs called single-nucleotide polymorphisms—SNPs, pronounced “snips.” For instance, I might have a CG—an inherited mutation—that makes me susceptible to diabetes type II (non-in-sulin-dependent diabetes), and you might have a CC, which is more common and makes it far less likely that you will get this malady. But merely having the SNP for diabetes doesn’t condemn me to have diabetes. The relationship between having most disease SNPs and having a disorder is still not entirely understood, but it’s known that having a mutant SNP for most ills is only one factor in actually contracting the disease—there are other SNPs and genes that come into play that either increase one’s chances or decrease them. Environmental factors also play a role in triggering a rogue SNP. In this case, if I have the CG for diabetes I may need to lay off the Cheetoes and Snickers bars, since obesity is known to trigger the SNP for diabetes type II. Other SNPs—for hair color, height, and my crooked second toe on my left foot, which my father and my two boys both have—make people different from one another from the moment they form in the womb.

With the emphasis in the media on DNA, you may think that genes are everything in an organism. They are not. The double helix may be a beautiful symbol of dignity, fear, and hope, revolving as a giant mobile in the lobby of deCode in Iceland and as a model made by Watson and Crick that still sits in a glass case at Cambridge. But DNA itself is nothing more, or less, than a storage bank of information. On its own, it can do nothing. It’s an utterly passive strip of mathematics that can no more cause a reaction than a skeleton key can by itself open a lock on a door. Most of the business of biotech involves proteins—trying to understand them, their structures, how they work, how they can be turned on and off by drugs. When the environment triggers a genetic response, genes are activated or shut down as a result, but it is a protein or proteins encoded by a gene or genes that actually does the job in reaction to an outside stimulus.

The biotech and pharmaceutical industries are spending billions of dollars to design new drugs based on genomics, the use of genetics and genes to track the mechanics of which genes and SNPs cause disease. Some drug design is extremely crude. For instance, no one really knows why ramping up serotonin in Prozac makes people less depressed. Some medications are better understood—such as Lipitor, which reduces the amount of cholesterol in the blood by inhibiting the activity of an enzyme required for cholesterol synthesis. Many drugs also have side effects because the drug compounds interact with proteins other than the intended target or cause problems even when they adversely impact their intended target. A few people suffer from severe side effects or die, sometimes because their own genetics are different from the norm. Figuring out these differences in an individual’s genome is called personalized medicine. In the future, people will have their genetic profile tested so that drugs and other medical treatments, diet, and exercise can be custom designed for each person—called pharmacogenetics. At least this is the hope.

The same technology may also be used to enhance lifestyle—designer mood drugs, drugs to boost memory. It also may lead to genetic discrimination, a scenario described in the director and writer Andrew Niccol’s Gattaca as “genism.” In this 1997 film, the main character, played by Ethan Hawke, is a “natural”—naturally conceived—in a world where genetically superior individuals get the plum jobs and the perfect mates. We will talk more about this later.

Another potential method to treat inherited diseases would be to alter the genes themselves, the hereditary DNA in each person called the germ line. This would involve going into a fertilized human egg and replacing, say, the SNP for diabetes—the CG with a CC—by deleting the deleterious SNP and inserting a correction. Researchers routinely use germ-line modification to alter the genes of plants and animals. If you want to make a mouse fatter, you insert a gene that causes obesity. Or if you want to stop a cancerous tumor regulated by a certain gene, you can turn off the gene by removing it from the germ line. Human ethics and legitimate fears about what would happen if we permanently altered a person’s germ line, which could be passed on to offspring, have prevented this sort of tinkering from happening in humans, though some scientists believe that human germ-line modifications are inevitable.

This is the story so far. It’s the first chapter, or, more likely, the prologue, of a very long book.