Below, Roxanne Khamsi shares five key insights from her new book, Beyond Inheritance: Our Ever-Mutating Cells and a New Understanding of Health.
Roxanne is a long-time health journalist who has reported extensively on the intersection of genetics and medicine for more than two decades. She is currently a contributing writer at The Atlantic and consistently covers new discoveries about how our DNA can influence our wellness.
What’s the big idea?
Most people think that our DNA remains the same throughout our lives. But in recent years researchers have uncovered an astonishing amount of acquired genetic changes that accumulate in us as we go about our lives. The discovery is changing all avenues of medicine, from heart health to immunity to aging.
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1. Men lose their Y chromosome.
Our bodies don’t always do a great job of hanging on to all their chromosomes, which are the bundles of DNA inside our cells. A curious scientist named Patricia Jacobs helped figure this out in the 1960s when she and her colleagues looked through a microscope at cells from people ranging in age from five months to 82 years. They discovered a very strange trend: As people get older, they often lose certain chromosomes. Women sometimes lose the X chromosome in some of their cells, and men likewise can lose their Y chromosome.
Much more is known about the phenomenon in men, and it’s shockingly widespread as they head into their golden years. A recent study of 200,000 men found that the proportion of individuals with significant loss of Y rose from 3 percent at age 40 to 44 percent at age 70. According to some scientists, it is the most common mutation to arise after birth in men.
The loss of the X and Y can happen in healthy people. That said, loss of Y has been linked to cancer and even Alzheimer’s. It’s not yet clear whether it contributes to these ailments directly or simply shares a root cause, and scientists are actively trying to figure this out.
2. Rogue cells can increase your heart risk.
We’re often taught to associate spontaneous mutations in the body with cancer. But new medicine shows that these DNA errors can also influence cardiovascular health. Scientist Sidd Jaiswal, currently at Stanford, and his collaborators showed that people with mutant populations of blood cells have a doubled risk of coronary heart disease and a more than doubled risk of stroke. He and his colleagues dubbed the condition “clonal hematopoiesis of indeterminate potential,” or CHIP for short.
CHIP is surprisingly common. It’s estimated that as many as one out of every five people in their seventies might have CHIP.
“New medicine shows that these DNA errors can also influence cardiovascular health.”
How does CHIP increase the risk of cardiovascular problems? Jaiswal has found some hints in animal studies suggesting that mutant blood cells exhibit an exaggerated immune response. In other words, they might be big drivers of inflammation. Increased inflammation is known to harden blood vessels and cause heart damage. Now that scientists know about CHIP and its possible effects, they’re starting to test certain hospital patients for the condition.
One prominent person who has CHIP is Michel Goldman. Goldman experienced a heart attack despite exercising regularly and eating a good diet. He’s not only a patient: Goldman is a pretty famous doctor himself—he once led a massive $2 billion health research initiative in Europe. So, he’s been very active in trying to understand what can be done about CHIP. He suggests that perhaps, in the future, people with confirmed CHIP should be offered anti-inflammatory drugs as a prophylactic treatment to possibly prevent cardiovascular disease, including heart attacks.
3. Vaccines mutate our genes (for the better).
We tend to think of DNA mutations as bad things. But the truth is, we cannot live without this change in our cells. In particular, we need our immune cells to be able to reshuffle their DNA and acquire new genetic alterations so that our immune system can come up with working antibodies to fight the viruses and bacteria we encounter.
In fact, certain people without the ability to mutate their cells are very vulnerable to getting sick from microbes. Patients with a condition called Hyper IgM can’t mutate their immune cells sufficiently, so they can’t make a broad enough range of antibodies. If untreated, they remain vulnerable to all sorts of rare infections, some of which can be deadly.
When a person with a robust immune system gets exposed to a pathogen, their immune cells undergo a process called “somatic hypermutation.” That helps the body refine the shape of its antibodies to bind better to deadly microbes and clear them away. This process is also what happens when we get vaccinated. These shots help our immune cells undergo somatic mutations, training them to produce the right antibodies. A strong immune system is a diversified one. Mutation is essential for a well-operating immune system.
4. Chemotherapy errors can be passed on to our kids.
There’s emerging evidence that what we experience in life can sometimes cause mutations in our reproductive cells, with possible consequences for our kids. This was a surprising insight that scientists gained when they looked at genetic information from a giant health database in England. The researchers detected mutational patterns associated with chemotherapy in several children. But this was very unexpected. None of these kids had ever had cancer. So why would their DNA show the hallmark effects of chemotherapy?
“The researchers detected mutational patterns associated with chemotherapy in several children.”
The children’s mutations were of a kind usually linked to a very well-known chemotherapy drug called cisplatin. The scientists went hunting for clues. They extended their look at the medical records to include those of the children’s parents. Suddenly, an answer jumped out at them. The fathers of these youngsters had experienced cancer and received treatment for it. It’s thought that the DNA changes in these men’s sperm from cisplatin had been passed on to their kids. And it’s not without possible consequences: there’s a worry that the cisplatin mutations could possibly raise the children’s lifetime risk of cancer and other diseases. The researchers say that it’s a good reminder that men planning to have a family someday should be offered the opportunity to bank sperm for future fertility treatments, like IVF, before they undergo cancer treatments.
5. DNA repair could be the key to longevity.
We’re learning that proper DNA repair inside cells might be very important to aging well. One person’s story is that of Michael Prescott. He was aging rapidly—looking decades older and suffering from cataracts and heart problems—and none of his doctors could figure out why. Michael did an extremely heroic thing: He took it upon himself to read as many scientific papers as he could, and he finally solved the mystery himself. He had Werner syndrome, a condition where mutations pile up faster than normal in the body and are associated with accelerated aging and, very tragically, early death.
The question is whether we can slow that mutation process to help people with Werner syndrome, and perhaps even push back against the problems of aging we all face. That is part of a larger lesson within Beyond Inheritance. By discovering how the mutations we pick up as we age affect our health, we might be able to design new treatments that target genes we haven’t considered as important in the past.
Scientists have studied the bowhead whale—the longest-living mammal on Earth—and believe its abundance of DNA repair enzymes could be the key to explaining its longevity. And they’re exploring whether we can apply this insight to help people age better. Ultimately, we need to talk about these DNA changes happening in us if we really want to modernize medicine.
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