What to read this week: Beyond Inheritance by Roxanne Khamsi

beyond legacy
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 not perfect. Many mistakes or mutations occur in the DNA of new cells: trillions of new mutations can occur in your body every day.

“Today you are a slightly different genetic version of yourself than you were yesterday, and tomorrow you will be different again,” Roxanne Khamsi writes in her book. Beyond inheritance: our constantly changing cells and a new understanding of health.

These mutations range from changes in a single DNA letter to the loss of an entire chromosome, such as X or Y. Many mutations are lost when cells die, but many mutations are passed on over time. By the end of your life, each of your cells may 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, noncancerous mutations also cause all kinds of problems.

Sometimes its effect is also visible. For example, purple “birthmarks” are the 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 colors that follow lines of growth known as Blasko 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 are different from each other. And these differences sometimes benefit some cells.

Take blood. When blood stem cells divide, one cell remains a stem cell and becomes a blood cell. Therefore, 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, over time, most of a person’s blood may be derived from mutants. This happens to at least a tenth of us by the age of 70, and that’s bad news because the mutant blood cells double the risk of heart attack and stroke.

What’s going on here is essentially an evolutionary battle between our cells, where those with a slight evolutionary advantage gradually become dominant. I was surprised, Khamsi explains, how many 19th-century thinkers, after Darwin, realized that evolutionary forces might also be at work within the body. But after 1900, with the rise of modern genetics, the idea was largely forgotten.

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

However, it’s not all bad news. To me, the most surprising chapter explains how new mutations can sometimes cure inherited conditions. There is also evidence that cells within the liver are essentially evolving to deal with conditions such as fatty liver disease. But accessory mutations are the exception rather than the rule.

I have some doubts about the writing and structure of this book. Chief among them is Khamsi – whom I have known since his employee days new scientists from 2006 to 2007, but have not been in touch for several years – writes in a style that insists on telling us a lot of things about people and places that are irrelevant to the content. For example, I don’t need to know that a researcher’s hair color is “salt and pepper.”

But here the message matters more than the writing style. This is an important book, which brings together a lot of different research from different fields to paint a picture that I think everyone should be aware of – especially those working in healthcare. That is, our bodies are made up of constantly mutating and often mutant cells, which compete with each other and sometimes do what is best for them rather than for us, even when they are not completely rogue and not cancerous.

“By abandoning the archaic idea that every cell has the same exact DNA and embracing the complex reality that each of our cells has a slightly different genetic code, we can usher in an entirely new era of medicine,” says Khamsi.

I’m not sure about the new age, but the implications are certainly deep. While Khamsi doesn’t put it this way, essentially his book is about how multicellularity gradually fails in each individual as cells become more diverse and more selfish. It’s a case of “things fall apart; the center can’t handle”.

It’s possible that this process is the root cause of aging, as Khamsi discusses. For example, many conditions characterized by premature aging involve DNA repair issues, meaning that mutations accumulate even more rapidly than normal. Furthermore, longer-lived species accumulate mutations more slowly than shorter-lived species.

Regardless of whether the creation of selfish mutations is the fundamental driver of aging or merely a contributor to it, this means that the idea that we will ever stop aging is nonsense. Sure, we may be able to slow down the accumulation of mutations with some 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 about 1500 mutations in each neuron analyzed. The great flood of mutation cannot be stopped for long.

At least, there is no way to stop the flood after our conception. Khamsi says that “human beings are the first living beings that want to shape their own genetic destiny”, but she does not reach the obvious conclusion that seems obvious to me: the only way to dramatically extend life span is to radically redesign the human genome to massively reduce the mutation rate.

I think it could be possible. But I wouldn’t describe it as extending the human life span. It is human to change. If this were ever done, these new creatures would no longer be human.

Three More Great Books on Heritage and Change

Power, sex, suicide: mitochondria and the meaning of life by nick lane

The mitochondria that generate the energy of human cells were independent bacteria before their symbiotic union with our ancestors made complex life possible. But as Lane writes, their otherness still shapes our destiny in every way.

The Mutant: On the Forms, Varieties and Errors of the Human Body by Armand Marie Leroi

Leroi writes, we are all mutants. For example, babies may also be born with one eye in the middle of their head. Sadly, cyclopia is fatal. However, such situations help us to learn about our development.

old man’s war by John Scalzi

Is old age always the end? not inside old man’s warA thoroughly enjoyable science-fiction romance. No spoilers, but I highly recommend it – and, surprisingly, the sequels are just as good, if not even better.