As you read this article, the cells in your body are dividing and the DNA in them is being copied, letter by letter. So long is the human genome—more than 3 billion letters—that even an astonishingly low error rate of one in many million letters could amount to 10 new mutations every time a cell divides.
Oh, perhaps you’re also catching some sun (ultraviolet rays) while you read this, or enjoying a beer (alcohol), or have recently been high in the atmosphere on an airplane (cosmic rays). Congratulations, you’ve given yourself even more mutations. In a typical day, scientists estimate, the 37 trillion cells in your body will accumulate trillions of new mutations.
Are you horrified yet? Good, me too.
But somehow we are not all walking bags of cancer. Somehow we accumulate bajillions of mutations and are, mostly, okay. How?
“It sounds very scary,” acknowledges Cristian Tomasetti, a cancer researcher at Johns Hopkins. “Fortunately for us,” he says, “the great majority of places where these mutations may hit don’t have important consequences.”
Imagine, if you will, that the human genome is like a finely tuned car. Many of the trillions of daily mutations in your DNA are like changing the tint of your car windows. It doesn’t really matter. Others may be so bad that they kill the individual cell, like if you took a valve out of the car engine. Very, very few changes would make the whole car run better. (Sorry to disappoint those who are wondering, Why don’t we all have superpowers? This is not X-Men.)
A small number of those mutations could strike in a cancer gene, making individual cells better at dividing and growing. But one mutation isn’t usually enough to make the cell cancerous. “Evolution has built in a formidable number of safety nets,” says Jan Vijg, a geneticist at the Albert Einstein College of Medicine. For example, a cancer cell needs to override the natural limit on how many times a cell can divide. It needs to escape “apoptosis,” or the cell’s tendency to self-destruct when something goes wrong. And it needs to evade an immune system that is constantly on the lookout for aberrant cells. A single cell must accumulate all these mutations to be become successfully cancerous.
Not all cells in the body accumulate mutations equally. A lot of this has to do with simply how frequently these cells divide. You’re constantly shedding the lining of your gut, for example, so those cells need to divide frequently to replace others.
Environmental factors play a role. For example, Tomasetti says, lung cells may come into frequent contact with tobacco smoke or pollution, which can cause mutations in their own right. Skin, on the other hand, is frequently exposed to sunlight. In one study, eyelid skin on middle-aged and elderly people—who have been through decades of sun exposure—had a stunningly high number of mutations: 60 to 180 in the genes of each cell.
Vijg has also compared the mutation rate in germ-line cells (sperm and eggs) with somatic cells (everything else, including your skin, liver, blood, etc.). Only the mutations in germ-line cells can get passed on to your children. And germ-line cells appear to have some way of suppressing mutations, perhaps through more robust DNA repair. The cells that make sperm, for example, are constantly dividing to make more sperm, but the mutation rate in sperm is less than one-tenth of that somatic cells. This makes sense in an evolutionary context: Mutated sperm are probably not very good in the race to fertilize an egg.
Once sperm meets egg, the fertilized egg begins to divide. And once it begins to divide, it begins making mistakes in DNA replication. “Even from the minute we’re conceived, our cells are accumulating mutations,” says Peter Campbell, a cancer geneticist at the Sanger Institute, who has studied mutation rates in the early embryo. (Campbell was also behind the eyelid-skin study.) Our cells continue to accumulate mutations over a lifetime. A typical blood cell from a 100-year-old person, Vijg says, contains 4,000 single-letter mutations and possibly hundreds of other kinds of mutations that are more difficult to detect through single-cell sequencing. Cancer is more common in the elderly because they have simply had more time to accumulate the right—or rather, wrong—set of mutations.
As humans age, cells in the body also become more different from each other. Perhaps half of your blood cells are descendants of a cell that acquired a certain mutation 20 years ago. The other half does not have this mutation. Imagine this process happening over and over again across decades, so that your body slowly becomes a mosaic of different cell groups, each with their unique mutations. We come to contain multitudes.