What to read this week: Beyond Inheritance by Roxanne Khamsi

Beyond Inheritance
Roxanne Khamsi, Riverhead Books (21 April)

There are around 30 trillion cells in your body and about 1 per cent of them get replaced every day. But this process is far from perfect. The DNA in new cells contains many mistakes, or mutations: there may be trillions of new mutations in your body every day.

“You are a slightly different genetic version of yourself today from yesterday, and will be different yet again tomorrow,” writes Roxanne Khamsi in her book, Beyond Inheritance: Our ever-mutating cells and a new understanding of health.

These mutations range from a change in a single DNA letter to the loss of an entire chromosome, such as the X or Y. A lot of mutations are lost when cells die, but many are passed on, building up over time. By the end of your life, each one of your cells may well have accumulated thousands of mutations.

Many people probably know that such mutations can result in cells growing out of control – becoming cancerous. But, as Khamsi describes, non-cancerous mutations cause all kinds of problems as well.

Occasionally the effects are visible. For instance, purple “birthmarks” are a result of mutations early in development that affect blood vessels, among other things. Mutations in skin cells can modify melatonin production, resulting in skin patches of different shades that follow lines of development known as Blaschko’s lines.

Similar things happen in every part of the body and at every stage of development. In other words, we are all mosaics, made up of patchworks of cells that differ from each other. And these differences sometimes give certain cells an advantage.

Take blood. When blood stem cells divide, one cell stays a stem cell and one becomes a blood cell. So, if blood stem cells divide at the same rate, they will have the same number of descendants. But mutant cells that divide at a faster rate have more descendants and so, in time, much of a person’s blood can derive from mutants. This happens in at least a tenth of us by age 70, and it is bad news because mutant blood cells seem to double the risk of heart attacks and strokes.

What’s going on here is essentially an evolutionary battle between our cells, where those that acquire a slight growth advantage gradually come to dominate. To my surprise, Khamsi relates how many 19th-century thinkers realised, post-Darwin, that evolutionary forces must be at work within the body, too. But after 1900, with the rise of modern genetics, this idea was largely forgotten.

There’s a growing list of these so-called clonal disorders, including at least some cases of endometriosis, where uterine cells grow on other organs. What’s more, we are probably just scratching the surface. Some kinds of mutations are still hard to detect and many organs are hard to study – you can’t easily sample heart or brain cells, say.

It isn’t all bad news, though. For me, the most astonishing chapter describes how new mutations can sometimes correct inherited conditions. There’s even evidence of cells within the liver essentially evolving to cope with conditions such as fatty liver disease. But helpful mutations are the exception rather than the rule.

I do have some quibbles about the way this book is written and structured. The main one is that Khamsi – whom I know from her days as a staffer at New Scientist from 2006 to 2007, but haven’t been in touch with for many years – writes in that style that insists on telling us lots of things about people and places that are irrelevant to the content. I don’t need to know that one researcher’s hair has a “salt-and-pepper” colour, for example.

But the message here matters far more than the writing style. This is an important book, bringing together a lot of disparate research from different fields to paint a picture that I think everyone should be aware of – especially those working in healthcare. That is, that our bodies are made of constantly mutating and often mutinous cells, competing with each other and sometimes doing what’s best for them rather than us, even when they don’t go completely rogue and turn cancerous.

“By letting go of the antiquated idea that every cell has the same exact DNA and embracing the messier reality that each of our cells has a slightly different genetic code, we can usher in a whole new era of medicine,” says Khamsi.

I’m not sure about a new era, but the implications are certainly profound. While Khamsi doesn’t put it this way, essentially her book is about how multicellularity in every individual gradually fails as cells become more diverse and more selfish. It is a case of “Things fall apart; the centre cannot hold.”

It is possible that this process is the root cause of ageing, as Khamsi discusses. For instance, a number of conditions that are characterised by premature ageing involve issues with DNA repair that mean mutations accumulate even faster than usual. Furthermore, longer-lived species accumulate mutations more slowly than shorter-lived ones.

Regardless of whether a build-up of selfish mutations is the fundamental driver of ageing or just one contributor to it, it means the idea that we will ever halt ageing is nonsense. Sure, we may be able to slow the accumulation of mutations by taking certain drugs and even fix some of them with gene editing, but all such efforts will ultimately prove futile.

Even if body transplants become a reality, the brain will still eventually fail. A study of people who died in accidents found around 1500 mutations in each neuron analysed. There’s just no holding back the great flood of mutations for long.

At least, there’s no way to hold back the flood after we have been conceived. Khamsi notes that “humans are the first living creatures that seek to shape their genetic destinies”, but she doesn’t go on to draw what seems to me the obvious conclusion: that the only way to dramatically extend lifespans is to radically redesign the human genome to massively reduce the mutation rate.

I think this could become feasible. But I wouldn’t describe it as extending human lifespan. To mutate is human. If this is ever done, these new beings will no longer be human.

Three more great books on inheritance and change

Power, Sex, Suicide: Mitochondria and the meaning of life by Nick Lane

Human cells’ energy-generating mitochondria were independent bacteria before their symbiotic union with our ancestors made complex life possible. But as Lane writes, their otherness still shapes our destinies in all kinds of ways.

Mutants: On the form, varieties and errors of the human body by Armand Marie Leroi

We are all mutants, Leroi writes. Babies can be born with a single eye in the middle of their head, for example. Sadly, cyclopia is fatal. However, such conditions help us learn about our development.

Old Man’s War by John Scalzi

Is old age always the end? Not in Old Man’s War, an enormously enjoyable science-fiction romp. No spoilers, but I highly recommend it – and, amazingly, the sequels are just as good, if not even better.