What to read this week: Beyond Inheritance by Roxanne Khamsi

Out of inheritance
Roxanne Khamsi, Riverhead Books (April 21)

There are about 30 trillion cells in your body, and about 1 percent of them are 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 than you were yesterday, and you will be different again tomorrow,” Roxanne Khamsi writes in her book. Beyond Inheritance: Our Constantly Mutating Cells and a New Understanding of Health.

These mutations range from changing a single DNA letter to losing an entire chromosome, such as an X or Y. Many mutations are lost when cells die, but many are passed on and accumulate over time. By the end of your life, each of your cells can accumulate thousands of mutations.

Many people probably know that such mutations can cause cells to grow out of control – becoming cancerous. But, as Khamsi describes, non-cancerous mutations also cause all sorts of problems.

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Many thinkers realized after Darwin that the forces of evolution must also work in the body
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Effects are sometimes seen. For example, purple “birthmarks” are the result of early mutations that affect blood vessels, among other things. Mutations in skin cells can modify melatonin production, resulting in skin patches of different shades that follow developmental lines known as Blaschk’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 a patchwork of cells that differ from each other. And these differences sometimes give certain cells an advantage.

Collect blood. When blood stem cells divide, one cell remains 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 offspring. But mutant cells that divide faster have more offspring, so over time much of human blood may come from mutants. This happens to at least a tenth of us by the age of 70, and it’s bad news because the mutant blood cells seem to double the risk of heart attack and stroke.

What is happening here is essentially an evolutionary battle between our cells, where those that gain a slight growth advantage gradually dominate. To my surprise, Khamsi recounts how many 19th century thinkers realized after Darwin that evolutionary forces must be at work in the body as well. But after 1900, with the advent of modern genetics, the idea was largely forgotten.

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

It’s not all bad news, though. To me, the most fascinating chapter describes how new mutations can sometimes correct inherited conditions. There is even evidence that cells in the liver essentially evolve to cope with conditions such as fatty liver disease. But useful mutations are the exception rather than the rule.

I have some doubts about the way this book is written and structured. The main one is Khamsi – whom I know from her days as an employee at the company The new scientist from 2006 to 2007, but we haven’t been in touch with them for many years – he writes in a 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 is a “salt and pepper” color, for example.

But the message here matters much more than the writing style. This is an important book that brings together a lot of disparate research from different fields to create a picture that I think everyone should be aware of – especially those working in the health sector. This means that our bodies are made up of constantly mutating and often rebellious cells that compete with each other and sometimes do what’s best for them rather than us, even if they don’t go completely mad and turn into cancer.

“By abandoning the outdated idea that every cell has exactly the same DNA and accepting the more unpleasant 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. Although Khamsi doesn’t say it that way, her book is essentially about how multicellularity gradually fails in each individual, as cells become more diverse and selfish. It’s a case of “Things fall apart, the middle won’t last”.

It is possible that this process is the main cause of aging, as described by Khamsi. For example, a number of conditions that are characterized by premature aging involve problems with DNA repair, which means that mutations accumulate even faster than usual. Furthermore, species with longer lifespans accumulate mutations more slowly than those with shorter lifespans.

Regardless of whether the accumulation of selfish mutations is the fundamental driver of aging or just one contributor to aging, it means that the idea that we will ever stop aging is nonsense. Sure, we may be able to slow down the accumulation of mutations by taking certain drugs and even fix some of them by editing genes, 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 about 1,500 mutations in each neuron analyzed. A great flood of mutations simply cannot be contained for long.

At least there is no way to hold back the flood after we were conceived. Khamsi notes that “humans are the first living creatures to try to shape their genetic destinies,” but he doesn’t proceed with what seems to me an obvious conclusion: that the only way to dramatically increase lifespan is to radically reengineer the human genome to massively reduce mutation rates.

I think it could be doable. But I wouldn’t describe it as an extension of human life. To mutate is human. If this ever succeeds, these new beings will no longer be human.

Three more great books on legacy and change

Power, Sex, Suicide: Mitochondria and the Meaning of Life by Nick Lane

The energy-generating mitochondria of human cells were independent bacteria before their symbiotic association with our ancestors made complex life possible. But as Lane writes, their otherness still shapes our destinies in many ways.

Mutants: On the Form, Varieties, and Defects of the Human Body by Armand Marie Leroi

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

Old Men’s War by John Scalzi

Is old age always the end? Not in Old Men’s Warimmensely enjoyable sci-fi romp. No spoilers, but I highly recommend it – and surprisingly, the sequels are just as good, if not better.

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