American Scientist

BEYOND INHERITANCE: Our Ever-Mutating Cells and a New Understanding of Health. Roxanne Khamsi. 304 pp. Riverhead, 2026. $30.

We tend to think of genetic disease as something we inherit, written uniformly into every cell—but many genetic diseases begin with mutations that emerge in only a subset of our cells. Although we each have a unique genome sequence, we are all composed of cells that carry slight genetic differences. Within our bodies, populations of genetically distinct cells can expand or outcompete others, echoing natural selection on a much smaller scale. Beyond Inheritance: Our Ever-Mutating Cells and a New Understanding of Health by Roxanne Khamsi explores the parallels between mutation and natural selection on the organismal scale to those acting on genetically distinct cells within our bodies, and the profound impacts these cell lineages can have on our health.

We each inherit a genomic sequence from our parents. But as cells in our bodies replicate, our DNA is not always copied accurately, creating genetic variation among cells within the same body. As Khamsi succinctly explains, “The body replaces 330 billion—about 1 percent—of its cells every day, so there are many opportunities for DNA copying errors to happen.” Just as evolution acts upon genetic variation between individuals in a population, somatic mutations generate variation between cells in our bodies, laying the groundwork for what Khamsi calls endoevolution, or the evolution of cells within our bodies. Changes in the frequency of cellular mutations are driven by cell reproduction and cell death. The mutations that occur during this process provide the genetic diversity upon which evolutionary forces such as natural selection can act.

Khamsi guides the reader through challenging genetics and evolutionary concepts with a series of concise stories. These include historical and modern tales of scientists making key treatment advancements, such as the development of a novel “lineage-based” vaccine targeting HIV, which consists of a series of shots carrying specific viral fragments aimed at stimulating the evolution of our immune cells to protect us from HIV. The author also follows patient experiences, diagnoses, and treatments, from the devastating tale of a pregnant mother with a rare blood disease caused by the expansion of a defective cell lineage, to the hopeful tale of two boys with severe inherited autoimmune disease who improved without treatment, due to a beneficial mutation that reversed the course of the disease and spread through their bodies with each passing year. Along the way, Khamsi thoughtfully braids together genetic and evolutionary lessons on inheritance, mutation, and natural selection, with each lesson building on the previous one.

Readers are eased into the idea of cells evolving within our bodies with an exploration of cancer through an evolutionary lens. Mutant cancer cells arise within our bodies and evolve and adapt to treatment due to their high mutation rates and natural selection, in the same way that weeds can develop pesticide resistance. This concept is presented to the reader before the idea that all the cells in our body may not be in coherent unison, as has been described since the beginning of the 20th century, when there was a strong biological movement “toward viewing each organism as a harmonious holistic system.” This view was compounded by the discovery of heritable units (genes) by Gregor Mendel, which “put an emphasis on how all somatic cells in the body contain the same genetic material.” Even now, when most of us hear the term “genetic disease,” we think about diseases caused by heritable genetic mutations, which are mutations that are present in every one of our cells because our parents gave them to us when we were just a single cell (that then divided to become the rest of our body). The author challenges our perceptions of personal genome sequences and genetic disease by explaining how we are each a mosaic of mutant cells, which lays the groundwork for a competition within us, where cells vie for the limited space in our bodies, tissues, and organs.

Although these concepts date back to the 1800s, they didn’t gain traction until the 1990s, when fruit fly geneticists discovered a concrete example of cellular competition, in which the presence of mutant cells near healthy cells could trigger the production of proteins that would wipe out the mutant cell lineage. Modern technology that allows scientists to sequence the genome of single cells has continued to enhance our appreciation of how cells with genetic differences interact with one another. The proliferation of some mutant cells can manifest as disease, including leukemia, heart disease, and even phenocopies of heritable disease—noninherited conditions that imitate inherited disorders, such as hemophilia and Down syndrome.

Khamsi emphasizes that, historically, “individuals who are genetic mosaics [have been portrayed as] medical oddities. But in reality, we all have some degree of genetic differences in our cells, no matter how small and nuanced, piling up over the years within our bodies.” Because we are all mosaics, and many of us are able to live relatively healthy lives, a major focus of the book is that not all mutations are bad for our health (even those that arise in disease-associated genes); indeed, many mutations have no health consequences at all. In fact, the influx of somatic mutations in some cells is critical to our health. The author highlights that the generation of new mutations is essential to a functioning immune system and, in some circumstances, can even rescue us from genetic diseases we inherited from our parents. Our immune system relies on genetic variation to produce a wide variety of antibodies so that our systems have a chance to protect themselves from quickly evolving viral and bacterial threats. As Khamsi writes, “It’s a beautiful system, fueled by mutation. We cannot survive without it.” New mutations can benefit our health in other ways, too, and have been found to have the ability to “self-correct”—a disease mutation that reverts to normal functioning and then, in rare cases, accumulates in enough cells to correct the course of the disease.

Of course, some mutations that arise during our lifetimes do get passed down to the next generation. These heritable mutations are the source of variation between individuals and the groundwork for evolution on a scale we are more familiar with. So how often do new heritable mutations arise? The rate at which new mutations are generated depends on the person and can be influenced by mutations themselves. Some men, referred to in the text as “hypermutators,” have a defective DNA repair gene that results in an excess of mutations in their sperm. Interestingly, Khamsi includes current research suggesting that the rates of new mutations in some somatic tissues are significantly higher than those in cells that divide to generate sperm and eggs. Genetic diversity is unmistakably being generated rapidly within our bodies, with a wide array of potential effects on our cells’ ability to survive and reproduce, and thus on our health as individuals. Health scientists are increasingly working to harness mutations for good, and perhaps to even revert disease-causing mutations back to healthy function.

Although the book highlights many devastating health consequences of our ever-mutating and mosaic genome, please don’t be in constant fear of the next mutation that will arise in your body. Humans have evolved an essential ability to repair mistakes in our DNA, and not only are most mutations not bad, the majority of mutations that occur are fixed within minutes of being made. Furthermore, throughout the book, the author expands on how researchers are trying to utilize their understanding of mutations and endoevolution to benefit our health, such as aiding the development of modern medical treatments, including cancer therapy, vaccine design, and organ transplants. Biologists have even started discussing how to maximize the efficiency of DNA repair machinery to reduce mutations and extend human lifespans.

With such a possibility in mind, Khamsi cautions, “After billions of years of life on earth, humans are the first living creature seeking to shape our genetic destinies. . . . However, we may need to ask whether it would always be wise to block or erase mutations with the possible gene-editing or drug interventions being contemplated.” The stories and lessons in Beyond Inheritance leave the reader with a new perspective that our personal genetic code is not fixed but rather a dynamic system fueled by mutation—a system that is constantly changing, with both harmful and beneficial impacts to our health.