Buried among the cascade of election headlines these past weeks, was a story as potentially transformative as the election of Barack Obama. As noted on NPR, in New Zealand’s National Business Review and others, is a report to be published in Nature that for the first time scientists have decoded a cancer genome (a genome is the entire DNA sequence of a cell—all 3 billion base pairs in this case). While this is a monumental step in the ‘War on Cancer’ President Nixon declared in 1971—a war, by the way, most expected to win easily within a decade—there is great potential for such information to be misinterpreted and over-interpreted by both scientists and the public, resulting in unrealistic expectations.
Our ability to grasp the meaning of this breakthrough lies in our understanding of cutting-edge work on the interaction between genes and environment that takes us from cancer genomes to a small isolated village in 19th century Sweden to women who were pregnant at ground zero on 9/11 to the children of Holocaust victims. In other words, this work requires us re-examine human responsibility to ourselves in a new light.
The chicken, the road it crossed, or both?
Virtually every cell of the trillions in your body has the same DNA—your entire genome’s worth. Cancer happens when the complex unwrapping and decoding of this DNA—telling a cell when and how much to grow where—goes awry, and cells grow out of control. Considering that most of our cells are growing non-stop, the amazing thing is that we don’t all constantly get cancer. Human beings have evolved a number of proofreading systems to identify and get rid of mistakes that would otherwise lead to cancer. Mistakes in those who do get cancer include mutations, or changes in the gene sequence, though several individual mutations must arise over time in order to ‘add up’ to a cancerous cell.
This means that the genome of one’s cancerous cells may be different (mutated) in these few, but clearly important ways, from the genome of your normal, non-cancerous cells—which is where the recent headlines come in. Recent technology that allows the relatively quick and inexpensive determination of entire genomes has resulted in the first case of comparing a single patient’s cancerous and non-cancerous genomes—comparing 3 billion base pairs and looking for a handful of differences—10 in this case.
This is, of course, exciting work, though several potential dangers lurk. Among them are:
1.) Inferring that these mutations cause cancer (they do not necessarily) and focusing on ‘correcting’ them as a major therapy (not the most promising of approaches).
2.) Forgetting that what causes cancer is often primarily human behaviors and environments in which we put ourselves or in which we are put.
3.) Assuming that genetic changes are the only manifestation at the cellular level that cause cancer
Just a brief word on (1) and (2) and then on to the more interesting (3).
The 10 mutations found in the cancer cells of the recent paper correlate to cancer in this one patient. We don’t yet know which mutation arose first (since the cells were donated by the patient after she had cancer and before she died) and which, if any, may have directly caused the cancer at the cellular and molecular level. This study and more like it on the way, will help physicians and scientists begin to see which mutations are more relevant, which will respond best to which therapies, which may have already arisen in apparently healthy cells. . . heady stuff, but a long way off.
Remember also that the genome the patient inherited from her mom and dad did not include the mutations that eventually caused the cancer; those occurred in the specific cancer-cells-to-be after she was born, presumably due to some environmental factors (She may have inherited the propensity to behave in certain ways or place herself in certain environments that make the occurrence of these mutations more likely or the propensity to be unable to effectively proofread or correct mutations, etc.).
The same 10 mutations occurring in someone else wouldn’t even necessarily lead to cancer. It would depend on the type of cell, when they occurred, and on the environment of the person. Why?
Environment here means not just what we usually think of—water, air, grass, trees, homes, etc—but all environments you and your cells experience from the moment of conception (and even beforehand in your mom’s egg and dad’s sperm). This includes things like what your mom smokes and eats when she’s pregnant, what diseases you and she have when she’s pregnant, and afterward. We’re used to considering these effects (see the warnings on alcohol bottles and cigarettes), and we’ve known for some time that they can directly lead to mutations in our DNA that may add up and lead to cancer.
The story of what we didn’t know is told in an impressive BBC/Nova collaboration. In a long-isolated village in Sweden exhaustive records were kept with generations of information on who died of what, when, and when famine or good harvests occurred. From these records researchers found that the age at which grandfathers started smoking bears a direct connection to the body mass of their grandsons; if grandmothers experienced famine prior to puberty, their granddaughters’ metabolism was affected.
The children of Holocaust survivors were previously thought to suffer post-trauma stress due to stories from their parents; now scientists are looking to see if these children may also have inherited epigenetic changes indicating that they may have been born with this stress. Pregnant mothers at ground zero on 9/11 who suffer post-traumatic stress gave birth to kids who do also.
Strikingly these affects are not manifest as mutations in the genetic sequence, but as epigenetic changes—changes that instead chemically modify the DNA so that certain genes are, or are not, expressed in later generations.
The mind-blowing point here is that your genome can respond to environmental change on the fly. That changes in the environment can lead to changes in how your genome is ‘read’ and that these changes can be inherited.
This entirely shifts the way we think about genomes and introduces a whole new way of thinking about how we care for our genomes. What we, our genes and cells that compose us, experience, can affect our children and our children’s children.
The implications:
1.) This is one great adaptive strategy. We don’t have to wait for DNA mutations to occur to change, but can respond quickly to our environments and we can pass these responses on.
2.) For the cancer study, yes, the DNA mutations might be relevant to what caused the cancer, though as, or more, important are the behaviors and environments of the individual and of that individual’s parents and grandparents.
3.) Could such epigenetic changes be important in diseases like cancer and autism? Preliminary work suggests the answer is yes.
And what about social and religious implications? The message is a strong one, a message that’s always been there, but is being powerfully reinforced by modern biology: take care of yourself, put yourself in good and supportive environments. It makes a difference, and not just for you.
