Masterminds: Genius, DNA, and the Quest to Rewrite Life. David Duncan Ewing

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.

       1 PROMETHEUS Douglas Melton

       There’s a natural fear of the unknown. On the

       other hand, I think it’s uninteresting to live in

       a society where one is so afraid of the unknown

      that you won’t try new things.

      —Douglas Melton

      Harvard embryologist

      Why did Prometheus do it? Myths about this god who gave fire to mortals against the express wishes of Zeus never explain his motive. But I’m going to make a guess. He had mortal children who were cold and tired of eating berries and gnawing on raw meat. And father Prometheus, who sat around Olympus with other gods warming his hands with glowing embers on cold nights, felt guilty. And that’s how we got fire.

      Prometheus paid dearly. Zeus punished him for breaking a command to keep fire in Olympus by chaining him to a rocky crag, where his liver was eaten every morning by an eagle, only to grow back by the next morning, so the screeching bird could tear it