The Case for Having Your Genes Sequenced

The genomic revolution started in 1964, when Robert Holley and his colleagues at Cornell and the U.S. Department of Agriculture deciphered the first gene sequence, indirectly "reading" the order of the four bases (adenine, thymine, cytosine, guanine) that pair up to make all genes, thereby allowing us to understand the blueprint from which each human is built. At first, the process was slow and costly (77 bases required four researchers and three years), and the prospect of ever figuring out the sequence of every human gene—the 3 billion bases of the human genome—seemed remote. However, aided by robotics, several teams raced to complete the job in the 1990s. By 2003, at a cost of $3 billion, most of one human genome had been sequenced.

The success of the Human Genome Project led people to speculate that someday every person would have his or her genome sequenced. At a cost of billions per genome, of course, it was an impossible dream. But beginning in 2004, a wave of next-generation sequencing technologies emerged, and costs began to drop 10-fold each year. Today we can sequence a million individuals' genomes for what it would have cost to sequence one person's genome five years ago. At a current cost of $5,000, it's become so inexpensive that some business models project that personal genome sequencing could be provided to individuals for free by third parties (insurers, employers, governments) who might be able to use the information from the sequencing as a way to reduce health-care costs. No matter who pays for it, as technology improves, the cost will continue to go down, likely to $100 per genome, and lower.

The benefits of genome mapping for some individuals are clear. Nearly every newborn today is screened for up to 40 genetic disorders—that's more than 4 million babies per year in the U.S. (although few of these tests sequence DNA). Before genetics, for example, a baby born with two damaged PKU genes would become mentally retarded. Now, babies that screen positive for this condition go on special protective diets. Carefully reading the genome has saved thousands from this and other painful conditions.

Over 1,500 disease-related genes have been discovered, knowledge that has improved medical diagnosis, treatment, and prognosis. Among the genes routinely sequenced in adults are the BRCA1-2 and neu/HER2 genes for breast cancer, multiple genes for colorectal cancer, the LQT1-12 genes for cardiac arrhythmias, and genes that cause a person to form blood clots more easily (like the factor V Leiden and prothrombin genes).

The message is not "Here's your destiny. Get used to it!" Instead, it's "Here's your destiny, and you can do something about it!" Diseases result from a combination of genetic vulnerability and lifestyle. If you know you have high risk of certain diseases, it's in your interest to know and practice the lifestyle that reduces your risk—and the younger, the better.

Personal genomics also helps doctors choose treatments, by identifying genes that make some medication options clearly superior to others. While "pharmacogenomics" is in its infancy, it is already helping many patients. Genetic tests are used to determine whether certain drugs are prescribed, and in what dose, for HIV-AIDS (the drug abacavir), psychosis (clozapine), blood thinning (warfarin), the heart condition called long QT syndrome (beta blockers) and cancer (imatinib, irinotecan, 5-fluorouracil, mercaptopurine, or tamoxifen). Recently, a gene variant has been identified that powerfully reduces the effectiveness of the popular anticlotting drug, clopidogrel. For the roughly 30 percent of people who carry the gene variant, higher doses of the drug are required: prescribing usual doses exposes the patients to serious, even life-threatening risks.

As low-cost genomics revolutionizes biological research, it promises significant public benefits. When the personal genomes and medical histories from much larger numbers of people become available, we expect much greater progress in identifying rare genetic variations that cause common diseases like cancer and heart disease. A growing number of people are volunteering to help this effort through programs such as PatientsLikeMe, The Personal Genomes Project, and regional biobanks. By sharing their medical histories and genetic information they hope to speed the search for cures and preventatives. These altruists deserve our support.

A common concern about new technologies is that they can broaden the gap between rich and poor. Genomics is no exception, but there is reason to believe that the poor could benefit from advances in the field. Infectious diseases are rampant in the Third World, and are a powerful barrier to people raising their standard of living and getting an education. Low-cost genomics enables the monitoring of new and old disease-causing microbes and the spread of drug resistance. This in turn permits deployment of optimal treatments.

It's a good thing to make genomes available to researchers, but potential problems exist as well. There is no more personal information than the sequences of your genes. Protecting the privacy of that data is essential to the future of genomics. If companies, health-care providers and governments collect and store our genomes and medical data, can they profit by controlling access to our genomes or cells? Do we have the time or know-how to control such access personally? If one's personal genome were known to insurers or employers, it could lead to discrimination. To address this, the Genetic Information Nondiscrimination Act of 2008 (GINA) prohibits health plans and health insurers from charging higher premiums, or making hiring or promotion decisions, based solely on individuals' genetic information. (GINA does not cover long-term care or life insurance, because of the concern that the people who purchased such insurance would be those who had learned from genetic studies that they were at risk for major diseases.)

As "the first genomic generation" we will set the rules that many future generations may follow. Will we treat our genomes like our faces, which we share publicly even though they reveal details about our health, ancestry, and personality? Or will we be forced to hide them from view? Knowing our DNA could make us think of ourselves more mechanically, and yet increase our humanity by embracing our diversity. It could render us less mysterious, yet more awe-inspiring. Our genomes are a vast future resource. How we handle them will define us as a species—not as a fuzzy average, but with our individualism evident in detail.