It boils down to this: Are you better off knowing or not knowing?  Decoding a genetic sequence can be very useful for a patient with symptoms doctors can't interpret, or for couples with troubling family medical histories who are thinking of having children.  But what if a person is healthy? Is there a compelling reason to know if your genes make you susceptible to a specific disease or condition?  Or are there some things you're better off not knowing?  On one side are scientists and doctors who see sequencing as another preventive diagnostic test. But others argue that the results are still too imprecise. How useful is it to know you have an increased risk of cancer when it could be twice the norm or 100 times?  And would you be able to handle the news, whatever it is?  This issue has implications not just for individuals, but for patient-doctor relationships and the health-care industry. Some fear the costs and strains put on the system by millions of otherwise healthy people who, as a result of sequencing, demand further tests and procedures that ultimately could prove unnecessary or, worse, harmful.  Atul J. Butte, who says healthy people should have their genomes sequenced, is division chief and associate professor at the Stanford University School of Medicine and director of the Center for Pediatric Bioinformatics at Lucile Packard Children's Hospital in Palo Alto, Calif.  Robert Green, arguing that the science is not yet at a stage that makes it practical for healthy people to have their genomes sequenced, is a medical geneticist at Brigham and Women's Hospital and Harvard Medical School in Boston and associate director for research at the Partners Center for Personalized Genetic Medicine. He directs the MedSeq Project, the first National Institutes of Health study to examine the impact of whole genome sequencing in the practice of medicine.  We live in an amazing time.  Very shortly, any individual will be able to know the sequence of his or her whole genome: This is the genetic recipe that guides the creation and functioning of our bodies. It's just a piece of what makes us unique individuals, but it's a critical piece.  What's to be gained from learning things about our bodies and our health that might scare us, but that we might not do anything about?  There are four important ways a healthy person can medically benefit from obtaining his or her whole genome sequence.  • Thousands of DNA combinations have been identified as indicators of susceptibility to specific diseases. Some argue that you might go through life worrying needlessly about a disease that never appears. On the other hand, spotting those DNA variants and recognizing whether you are at risk can lead directly to early diagnoses and preventive strategies.  • Couples planning families can find out when they carry genetic risks for severe disorders and so make more informed choices: to have a baby together and hope for the best, for example, or to adopt.  • Doctors can better determine what drugs will be most effective for a patient, at what dose, and what drugs to avoid.  • Genome sequencing also can help in the diagnosis of illnesses yet to be identified.  Genome sequencing isn't perfect. There are mistakes. But not many. We can currently expect one misread bit of DNA among hundreds of thousands. Other common preventive medical procedures aren't free from errors either: Mammography and Pap smears have high overdiagnosis rates, and PSA testing (prostate specific antigen) is unreliable, yet we typically accept these problems.  A researcher with a DNA sequencing machine  Moreover, continuing research will certainly identify more of the inaccurate and "missing" bits, leading to better clinical interpretations.  Some people believe that the practice of medicine isn't ready for widespread use of genome sequencing. Multiple vendors now offer sequencing for close to $1,000. Sequencing in a medically regulated setting costs more, but is comparable to the cost of a colonoscopy.  As sequencing becomes more available, there are naturally anecdotes of doctors having neither the time nor ability to deal with the results. But doctors will adapt, and tools will be built to help doctors and patients interpret genomes. Just because some doctors aren't up on the latest tools doesn't mean that we should abandon those tools altogether.  Some also argue that the use of sequencing by healthy people could lead to more unnecessary tests and procedures. But this can be avoided if patients and doctors better understand the actual post-test risks implied in the sequencing results.  Orders for follow-up tests should come only after a serious weighing of the actual risk and the severity of the disease in question.  There are limits. Despite the incredible science behind sequencing, we won't be able to predict every possible condition in one's lifetime. Behaviors, environment and other factors are involved. But there are already individuals who have had a whole genome sequenced, and who learned the pharmacological, environmental, medical, or behavioral changes they could make to "compensate" for their genome.  There is no gene for compliance; it can require difficult changes to improve one's health. But for many people, that genome sequence may provide the crucial first step to move from "knowing thyself" to "helping thyself."  Dr. Butte is division chief and associate professor at the Stanford University School of Medicine in Stanford, Calif., and Lucile Packard Children's Hospital in Palo Alto, Calif. He is a founder and adviser to Personalis, a company that offers genome interpretation. He can be reached at reports@wsj.com.  MEDICAL SCIENCE can now sequence healthy individuals, but we cannot yet say that this will be beneficial.  Genome sequencing is starting to provide benefits for some people with rare genetic disorders and previously undiagnosed clinical conditions, and for determining treatment of some forms of cancer. Technological innovators are driving down sequencing costs and improving accuracy; researchers are refining variant databases and enthusiasts are exploring their own DNA seeking insights about their health and ancestry.  Most of us agree that in a few years, affordable genomic and epigenomic analyses of healthy individuals will allow for more individually tailored disease prevention and pharmaceutical treatment, as well as broader options for preconception and prenatal screening. But some serious challenges remain before this can be done safely.  One problem is that medically dangerous genetic mutations are quite rare in healthy individuals, but finding them today would still be enormously expensive. This year an entire genome will cost somewhere around $5,000 to be sequenced, analyzed with bioinformatics and interpreted. And while there is much to find in each genome that can reflect subtle health risks or aid in reproductive planning, we currently estimate that less than 2% of healthy people will have a dangerous and well-recognized DNA mutation that might cause a doctor to initiate surveillance or treatment. That means spending $250,000 to find even one such individual.  A technician examines DNA sequencing gel  But what if tomorrow, sequencing and interpretation cost only pennies and we sequenced 1,000 individuals to find 20 with dangerous mutations? We still might do more harm than good for some of them because known mutations may or may not carry the same risk in the absence of family history. If a healthy person without a family history has a well-recognized heart-rhythm mutation, should we send them home with reassurance or surgically implant a pacemaker?  Finding well-recognized disease mutations in healthy people is just the tip of the genomic iceberg. We all have unique or novel mutations in disease-associated genes. I have 14 such mutations in my own genome! But the smartest geneticists in the world cannot always agree as to whether a novel mutation is dangerous. If a healthy person without family history has a novel mutation in a cancer predisposition gene, should we take X-rays every year for the cancer that might never appear? Should we do the same for their parents, brothers, sisters and children that carry the same mutation?  Injecting so much uncertain genetic information into the doctor-patient relationship could create legions of "patients in waiting" leading to unnecessary tests, harmful outcomes and lifelong anxiety. As private software companies compete to provide more genomic "findings" to a medical culture that is trained to search for diagnostic fire when they smell the smoke of disease risk, there are potential benefits. But there is also a real possibility that medical resources will be squandered and patients could be harmed.  Perhaps we all underestimated how complicated it would be to move genomic knowledge into the practice of medicine and public health. Now is the time to make sure we get this right through rigorous basic and clinical studies that define which mutations are dangerous, and distinguish useful from unnecessary interventions. Soon, genomic insights will give us early warnings about life-threatening illnesses that we may be able to prevent. Soon, standards will be available to guide doctors about which findings are meaningful and which are not.  Soon, there may be evidence to support the benefits of screening healthy individuals. But not today.  Dr. Green is a medical geneticist at Brigham and Women's Hospital and Harvard Medical School in Boston and associate director for research at the Partners Center for Personalized Genetic Medicine. He directs the MedSeq Project, the first National Institutes of Health study to examine the impact of whole genome sequencing in the practice of medicine. He can be reached at reports@wsj.com.
Yes, proponents say, because more knowledge means better health. But others worry that the results may contain too many errors.