Acting on Information
Confession: In college, I got a D in genetics. You could say that when it came down to me and genetics, genetics was dominant and I was recessive — and I receded week by week to the back of the class. Genotype was just not my type. My thinking at the time boiled down to, “Hey, knowing the minutia about Mendel and his peas won’t amount to a hill of beans for me. I’ll never use this stuff.”
Fast forward to 1990 and the launching of the 15-year, $3 billion Human Genome Project (HGP). Scientists were lathered up about plans to map and sequence the human genome, meaning they were going to diagram the complete set of human chromosomes and genes. “Big deal,” I thought, “these guys are making a map. This is another example of obsessive scientists knowing more and more about less and less. I’ll never use this stuff.”
Fast forward again to 2003. The HGP is done, two years ahead of schedule. They did it! Scientists actually mapped out the 30,000 to 40,000 genes of the human genome. They found the sequence of 3 billion base-pair “letters” of human DNA (deoxyribonucleic acid).
DNA is the helical molecule that makes up genes. It holds the code for every protein and enzyme made by the human body and dictates how the body runs — even the smallest irregularity in DNA can cause disease. In many ways, our health is rooted in this molecule.
Just when I am about to say, “I’ll still never use this stuff,” my daughter, Kate, develops a pre-diabetic condition. Doctors say she can avoid developing diabetes if she exercises more, loses weight, and changes her diet.
I’m thinking, “Wait a minute. I thought if you got the genes for diabetes, you get the disease.” Kate’s biological parents (she is adopted) must have the diabetes genes, which are expressing themselves in Kate.
Turns out I’m wrong. Having the genes does not always mean getting the disease, at least not with some diseases. This is not hot news; apparently science has known this for years. But what’s now becoming increasingly evident to folks like me is that getting or not getting a hereditary disease or condition isn’t just a matter of dumb luck. What we do (or don’t do) to our bodies — right here and now — can make all the difference in how our genes ultimately behave, or “express.” In short, our everyday choices can effect whether countless tiny genetic “switches” in our DNA are turned on or off, and by extension, whether we develop or successfully avoid all kinds of hereditarily influenced health woes.
Acting on Information
The excitement about the HGP is creating an ever-greater buzz, and increased popular understanding, about the direct way that lifestyle and environmental factors can and do influence genetic expression. As a result, I realize, it is becoming increasingly inevitable that I probably am going to use this stuff.
The insights coming out of the HGP are huge. More than 12,000 mutations have been found on more than 600 genes, and new mutations are discovered — and widely reported — almost weekly (the Wall Street Journal recently reported that scientists have identified a gene mutation that appears linked to binge-eating). These discoveries are helping scientists to understand illnesses — and even some behaviors — at a molecular level. Over time, the same discoveries are also leading toward the development of improved treatment, prevention strategies and more accurate diagnostic tests, with life-saving results.
As science reveals the tiniest details of DNA, our knowledge about why certain treatments work for some and not others is rapidly advancing. Genetic testing, too, has evolved. Previously applied mostly for unfortunates already affected by rare disorders or for expectant parents concerned about the health of their unborn children, it is now gradually going mainstream, and being aimed not just at sick people but at healthy people who want to stay that way.
Much of the current excitement in this area revolves around predictive genomic testing — tests that help identify people who are at risk of getting a disease. The idea is to give individuals and their doctors information that can help them take precautionary action (such as nutritional, exercise and lifestyle adjustments) early, before symptoms have a chance to appear.
Predictive genomic testing is exciting to science and health professionals alike because it promises to help them find ways to modify human biochemistry long before potentially dangerous hereditary genes are “switched on” and sometimes-irreversible diseases take hold.
Most of the common disabling and deadly degenerative diseases, including cardiovascular disease, cancer, Alzheimer’s disease, and adult-onset diabetes are thought to be the result of interactions between genetic and environmental factors. As noted, scientists also know that many genes can be “switched on or off” by environmental cues. What this means is that our genes have a dormant predisposition to express a particular trait, and specific circumstances or behaviors can either trigger or discourage the eventual expression of that trait. Common examples include how smoking activates genes that contribute to a variety of cancers, how excess salt may switch on genes that contribute to hypertension, and how obesity contributes to the development of diabetes.
Dozens of predictive tests are already available (some only in research programs), and as more disease genes are discovered, their numbers will undoubtedly expand. Many genetics experts warn that it is too early to get doctors and patients overly excited about predictive tests, because the tests are by no means simple or 100 percent effective, and in many cases, a simple family history can be as useful. Plus, there’s not full agreement on how to interpret or react to the results of all these tests once they are in.
Still, some doctors are finding that advance warning about potential genetic risks is sometimes exactly what it takes to spur otherwise apathetic patients into self-care measures they would otherwise shrug off, such as smoking cessation, diet modification and exercise routines.
Affecting Genetic Expression
Warding off unnecessary suffering and disease is the whole focus of emerging, cutting-edge scientific disciplines like pharmacogenomics (the study of how an individual’s genetic inheritance affects his or her body’s response to drugs) and nutrigenomics (the study of how individual dietary and nutritional factors impact genetic expression and disease). Both these disciplines have gotten a huge boost from the HGP, and are now actively informing public-health policy and food technology as well as the pharmaceutical and nutritional industries.
Many of their most promising impacts are just starting to trickle down to consumers, but again, the principles behind these sciences are compelling enough for everyday people to sit up and take notice now. For example, it is known that the presence of naturally occurring chemicals in our diet can alter our gene expression in a number of ways, and that specific chemicals affect genetic expression differently in different individuals. In other words, for people who share a particular genetic pattern, the intake of a certain food-based chemical (such as a specific mineral or lipid) will encourage positive genetic expression, while in others, the presence can be neutral or antagonistic. This means that certain foods, drugs and dietary approaches that are healthy for some people are potentially dangerous for others.
The human diet requires about 40 micronutrients. Micronutrient deficiencies can cause DNA damage and are associated with a number of diseases. For example, a folic acid deficiency, which affects about 10 percent of the U.S. population, can cause chromosome breaks in the DNA, which may in turn lead to colon cancer and heart disease.
Poor diet is to blame for some cases of micronutrient deficiencies, while others are due to polymorphisms (variations in DNA base-pair sequences) in genes that produce enzymes involved in micronutrient metabolism. Researchers have found about 50 human genetic diseases — all attributable to enzyme polymorphisms — that can be remedied or improved with high levels of vitamin supplements.
“There is increasing awareness of the potential for genetic variation among individuals to influence both nutrient requirements and biological responses to nutrient intake,” says Ronald Krauss, MD, director of the Lipid and Chronic Disease Research Core at the Center of Excellence in Nutritional Genomics at U.C. Davis.
Experts like Krauss are already envisioning a near future where consumers will be able to obtain silicon “nutrition chips” with their genomic information encoded in them. By taking the chip to the grocery store, for example, they’ll be able to make precise decisions about which foods and ingredients they should avoid, which they should eat more of, and how they should supplement with additional vitamins, minerals and enzymes.
According to Ray Rodriguez, professor of molecular biology at U.C. Davis and chief scientific officer at the Center of Excellence in Nutritional Genomics, there’s a growing number of people interested in accessing and applying this information as it becomes available. “We’ve seen clearly that it is possible to eat yourself into chronic disease or optimal health,” he says, “and with more people wanting to achieve the highest possible quality of life during the second half of their life, the interest in eating healthy is not going to be a fad.” Rather, he says, it’s a paradigm shift, and it’s here to stay. “As this type of genetic information is made more widely accessible,” Rodriguez asserts, people are just going to keep getting smarter.”
Even before genomic testing and reporting does become widely available, we can start incorporating the lessons of early identification and proactive intervention in order to give ourselves as much genetic “health insurance” as possible — simply by taking common-sense measures, like exercising regularly and eating wholesome, natural foods high in nutrients and low in unhealthy fillers and additives. As we learn more about our genetic and metabolic profiles, we can then begin using customized eating and supplementation strategies to enhance our diets even further.
The HGP has shown us that more than 99 percent of human DNA is identical among all people. Astonishingly, the mere fraction of 1 percent that is different is responsible for creating all our individual variety. The most common variations are known as single nucleotide polymorphisms, or SNPs (pronounced “snips”). These are places where the DNA sequence varies by a single base, or DNA letter. Nearly 3 million SNPs have already been identified.
Scientists use their knowledge of SNPs to scan the entire genome, looking for chromosomal regions that are statistically associated with disease. Researchers can then refer to the human genome map to find the genes in those regions and narrow their search for the disease-causing alterations. SNPs promise to help scientists more accurately pinpoint the genetic differences that predispose some people (and not others) to specific diseases. These same differences also could help explain why certain medicines affect people very differently.
It is probable that genomic testing will soon be part of a comprehensive healthcare effort to predict not only which of these diseases we are most at risk of developing but also what foods, supplements, drugs, and types of exercise are best for optimum health and disease avoidance. Instead of relying on randomized studies involving large patient populations to determine care for a patient (which can’t possibly take into account or track the impact of individual genetic variances), doctors will have access to sophisticated diagnostic and therapeutic tools individualized for each patient. Disease definitions will be broadened and categorized, resulting in hundreds of distinct types of asthma, arthritis, or dementia, for example — each easily recognized by new testing and then treated specifically for its variation. New treatments, as well as old, will be tailored to these individual, better-genetically-defined patients, resulting in more effective care.
Not There Yet
While it is true that such wonders related to predictive genomic testing are in your future, the key word, in most cases, is still future. You can already get some genetic tests based on bucal-smear samples simply by ordering them online, gathering some DNA by swabbing the inside of your cheek, and returning your sample to a lab. However, most experts believe that direct- to-consumer genetic testing is a bad idea and potentially dangerous. They say there is considerable risk of getting back incomplete, confusing or misinterpreted results.
Then there’s the problem of deciding how to respond to the results you get. Some experts are concerned that uncounseled consumers will be unnecessarily upset and become vulnerable to commercial exploitation if their fears of possible genetic outcomes prompt them to take ill-advised courses of action (e.g., getting swindled into buying questionable supplements, embarking on extreme diets, etc.).
Yes, it would be nice to submit one tiny DNA sample and get an immediate printout of everything you should be eating and avoiding, but as one expert puts it, “We’re not at Gattica quite yet.” Until testing is ready for prime time, most experts emphasize the importance of health monitoring, family histories and regular medical tests to identify problems that could contribute to genetic triggers.
This type of anecdotal and clinical knowledge about your genetic “weak links” can help you determine which lifestyle modifications are most likely to help you work around potential problems. For example, if you know that arthritis or osteoporosis (inflammatory conditions) run in your family, or you have noticed that you are prone to joint trouble, you may decide to take special precautions to avoid pro-inflammatory factors (such as sugar or foods to which you have sensitivities) in your diet. You may also look for foods and natural supplements that help moderate inflammatory effects, and you may seek out regular lab tests to help you track how your body is faring.
Whatever genomic testing you do decide to do should be ordered and interpreted by your doctor or a genetic counselor (see sidebar). You may be able to get a certain amount of basic genetic data from a direct-to-consumer lab. But don’t be fooled into thinking you can do a mouthwash swish, mail it in, and find out precisely what diet you should eat, what vitamins and drugs to take, etc. Most genetic counselors insist the process isn’t that direct.
“Research is proceeding at a rapid rate, but it is not yet at a point where many of the genomic tests are easily utilized by the public,” says Bonnie LeRoy, MS, associate professor in the department of genetic cell biology in the Institute of Human Genetics at the University of Minnesota.
“Keep in mind that when scientists look at genomic profiles, they are looking at the subtle effects of 200 to 300 genes — we don’t even know all of the combinations yet — and how they work together to make a person be at a slightly higher or lower risk,” says Katherine Schneider, MPH, senior genetic counselor at the Dana-Farber Cancer Institute at Harvard University. “I don’t think the data supports claims that we can look at a genomic profile and give an accurate prediction about heart disease, diabetes, and the like. In two to five years, maybe.”
There seems to be little doubt that predictive genomic testing, in the context of genetic counseling and the full spectrum of genetic testing, will be a boon for patients trying to get back to health or avoid disease in the first place. It’s just a matter of time.
“Where cancer testing was 10 years ago, at the beginning stages of being useful clinically, that’s where genomic testing for psychiatric disorders, diabetes, heart disease, and Alzheimer’s is now,” says Bea Leopold, MA, executive director of the National Society of Genetic Counselors. “Today, predictive genetic testing for breast, prostate, colon, and other cancers is good, and that’s where testing for these common but multifactorial adult disorders will be. That’s where the future is.”
To be sure, the mapping of the human genome is setting off a revolution in science and industry and an explosion of possibilities in healthcare. But, as with all revolutions, some dust has to settle before the possibilities of science will play in Peoria clinics.
“The publication of the human genome is only the first step in a process,” says Cate Walsh-Vockley, MS, CGS, certified genetic counselor at Mayo Clinic in Rochester, Minn. “Before we can reach a point of applying all these discoveries clinically, we have to figure out what each gene does and how it interacts with other genes. There’s a lot we have to understand before we jump in and start testing people.”
In the meantime, most experts agree, it is worthwhile for average folks to prepare by getting familiar with the genetics concepts and the state of genomic science. It’s worth wrapping our head around the implications of the HGP and the wonders of our own physiological and biochemical individuality. It’s absolutely worth understanding how simple life choices we make now can flip (or not flip) genetic switches that could make or break our health down the road. Because chances are good, sooner rather than later, we‘re all going to use this stuff.