blueprints drawn up: the map of himself, his entire human genome. The Harvard professor of

Ten years ago, it cost billions of dollars to map a single human genome. Today, it’s about $20,000 and likely to get even cheaper. If the average consumer can afford to have her own genetic map drawn up, what will it mean for medicine and how we approach our health care? n early 2008, Henry Louis Gates Jr. stepped off his flight at LaGuardia Airport and began the process of having an elaborate set of blueprints drawn up: the map of himself, his entire human genome. The Harvard professor of African American studies had at the time just hosted PBS’ successful miniseries, The miniseries, which Gates jokingly calls “Roots in a Test Tube,” traced the genealogical and genetic heritage of prominent figures and celebrities such as Oprah Winfrey, Morgan Freeman, Tina Turner and Chris Rock. Also on Gates’ flight were officials from the Cambridge, Massachusetts-based genetics company Knome, who told Gates they were interested in working with him on other projects involving DNA testing. Already prompted by the mini-series’ fans to do a show about all Americans, Gates told the Knome representatives that this time he wanted to make a PBS series based on testing the full DNA (or “genome”) of some of his guests. Every living thing on Earth is built from instruction manuals—an organism’s genes—found inside its cells. The complete set of instruction manuals is called a genome. For humans, the complete set is 6 billion characters long. We all inherit half of our body’s instruction manual (3 billion characters) from our mother and half from our father. When these strands bond together, the connections create units of information called “base-pairs.” Base-pairs can take on one of four values, signified by the names of the molecules from which they’re made: A, C, G or T. Sequencing a person’s genome means discovering the value of all 3 billion DNA base-pairs—every A, C, G and T—in your body’s instruction manual. It’s the full host of biological blueprints that encodes uniquely who you are. In 2003, only one human genome had been sequenced in the world, and it cost 50 cents per character. Today, just seven years later, the price has dropped to an astonishing 1/300,000 of a dollar per character. Within two to four years, because of rapidly advancing technology and economies of scale, the price is expected to fall by another factor of 10 or more—bringing the total cost of a full genome down to about $2,000. The era of affordable genomes hasn’t yet arrived, but it isn’t far off—and mapping personal genomes at the price point of a laptop computer will change the face of medicine and, in a sense, the world. or his 2009 series Gates traced the genealogical and genetic heritage of guests such as Eva Longoria Parker, Yo-Yo Ma, Meryl Streep, Stephen Colbert, Dr. Mehmet Oz and figure skater Kristi Yamaguchi. And, although Gates wanted to do full genomes of two of his guests, his scientific advisers recommended instead sequencing the genomes of both Gates and his father, 97-year-old Henry Louis Gates Sr. (Scientists hadn’t yet sequenced any African American’s genomes, nor had they sequenced a father-son pair.) In fact, perhaps the most heart-wrenching moment in comes when the program’s genetic experts subtract Gates Sr.’s 3 billion DNA base-pairs from Gates Jr.’s genome. And there, in bold blue and yellow lines, lies the stark genetic outline of the younger Gates’ mother, who died in 1987. “I put my father in this series,” Gates says. “And the big shock is, I got my mother back.” What Gates discovered about his mother was largely symbolic. He, like everyone, carries the blueprint of each of his parents inside his every cell for every moment of his life. However, Gates also learned a boatload of information about his own life and health. A person’s genome carries crucial information about individual weaknesses to disease, susceptibility to various cancers, the effectiveness and ineffectiveness of various drugs and, ominously, some of a person’s more likely ultimate causes of death. In 2000, President Bill Clinton announced that the government had created the first draft of the entire human genome. Ten years later, scientists still haven’t been able to apply the $3 billion Human Genome Project to curing some of our deadly, elusive diseases. In May, genomic researcher J. Craig Venter announced that he and his colleagues had created the first synthetic cell. Using chemicals, they recreated the genetic code of a species of bacterium and then transplanted the manufactured genome into a closely related bacterium. Then the synthetic DNA took over. The genetic counselors Gates hired for told him he carried an innate resistance to certain forms of malaria and that caffeine breaks down quickly in his digestive system. So coffee has less effect on him than it does on most people. “For years I hadn’t drunk [coffee] after noontime, being afraid it’d keep me awake,” he says. But emboldened by his genome results, Gates tried drinking a cup of joe one night before bed. “I went right to sleep,” he says. Other than a variant of sickle cell anemia that makes him more susceptible to a stroke at high altitudes, Gates also learned that no unexpected ticking time bombs awaited him. Thanks to the lack of grave surprises in his DNA, Gates joined a project by his colleague George Church of Harvard Medical School that posts a patient’s entire genome on the Internet (at ) for scientists—and anyone else—to study. The need for publicly accessible genomes to compare and study became evident in An initial analysis of a single character in one of Gates’ genes suggested he also had an exceptionally good ability to digest dairy products. But Gates is lactose intolerant. “I’m the one with the stomach for 59 years,” he said. “I know I can’t drink milk.” It was only on a closer examination of Gates’ genome—enabled by more detailed analysis of his own genes and comparisons to other peoples’ genes—that Knome researchers discovered the source of Gates’ difficulty with dairy products. s particular DNA blueprint, they discovered, also makes it hard for him to process a dairy digestive by-product, called galactose. This is why he can drink plenty of coffee, but not with milk. ne of the first full families—mother, father and children—to sequence their genomes was the West family of Cupertino, California. John West, the father, is a former executive of one of the leading genome sequencing companies in the world—Illumina of San Diego. West, his wife, Judy, and children, Anne and Paul, had blood samples drawn late last year and in January received an iMac that contained all 24 billion A’s, C’s, T’s and G’s which represented the whole West family genome. Although the family is keeping the kids’ genomic results private, 17-year-old Anne has given a public presentation about inheriting a genetic defect from her father that in 2004 resulted in a trip to the emergency room for him. Raced to the hospital with a blood clot in his lung, John West endured a painful and frightening few days staring at his own mortality. But now he and his daughter know the likely cause of his hospitalization. They also know the diet to follow and medications to take to drastically reduce the chances of anything like this happening to either of them in the future. West says his Illumina genome fortunately revealed no bombshells other than the known “misspelling” in a gene of his called “Factor 5.” Such genetic errors, resulting from single-character transcription mistakes soon after a child is conceived in the womb, are sprinkled throughout everyone’s genome. Most DNA mutations are harmless. But just one well-positioned mistake—imagine a car repair manual containing the typo “plug the fuel line” instead of “plumb the fuel line”—can wreak havoc. Many will remember Dolly, a Finn Dorset ewe that in 1996 became the first mammal to be successfully cloned from an adult cell. She was cloned at the Roslin Institute in Scotland and lived there until her death in 2003. Before that, however, a tadpole was the first vertebrate to be cloned, in 1952. Since Dolly’s death, many animals have been cloned, including a camel and a water buffalo. Spitting isn’t au courant at New York Fashion Week, but that’s what notables such as Rupert Murdoch and Ivanka Trump were doing in 2008 at 23 and Me’s genetic testing spit party, hosted by founders Anne Wojcicki (wife of Google co-founder Sergey Brin) and Linda Avey. The driven by National Geographic Explorer-in-Residence Dr. Spencer Wells, is “seeking to chart new knowledge about the migratory history of the human species.” If you wish to participate, a $99.95 kit is available to test your DNA and determine your ancestry along your maternal or paternal line. Two shows on television this spring, and featured prominent people who went looking for their lineage. NBC’s used old-fashioned, document-based genealogy, while PBS’ paired genealogy with genetic testing. Talk about one-of-a-kind art. DNA 11 takes a sample of your DNA and reproduces it in color on a canvas you can hang on your wall. You can even mingle your DNA with your spouse’s, for a truly unique anniversary gift. It’s genetics as home décor. After years on the road with Black Sabbath and a 40-year “bender,” how has Ozzy Osbourne survived? That’s what DNA research company Knome is going to try to find out by sequencing the 61-year-old’s entire genetic code. The company is reportedly interested in Osbourne because of his “extreme medical history.” Although genetic testing is still in its infancy, West says there is one way to enjoy access to every genetic test in the world—and every one yet to come. “There are hundreds of genetic tests. And if you were to take every single one of them separately, it’d cost you a fortune and you’d have to pay attention to all these individual pieces,” he says. “The advantage of having your genome sequenced is you’re doing all possible genetic tests all in one shot.” Mike Spear, communications director for Genome Alberta, a genetics funding organization in Calgary, Canada, has had small snippets of his genome tested by genetic-test companies deCODE and 23andMe. He learned, for one, that he’s at high risk for early onset Alzheimer’s disease. And he already knew that longevity runs in his family—a grandmother lived to be 101 and his father is still in the work-force at age 85. “So I’m going to live long, but the last 30 years will be in a corner,” he says. He also says, though, that most genetic test results just weigh the dice a little, so it’s important not to get too carried away. Spear learned, for instance, that he has twice the risk of baldness compared to the average man. “Your genome is what you are, but there are so many factors involved,” he says. “So I’m at higher risk for baldness, but … I have a full head of hair, and I’m 56. I’m at very low ‘risk’ for asthma, but I have always been an asthmatic.” Spear says anyone who already tends toward hypochondria or excessive worrying might want to think twice about personal genome sequencing or genetic testing—especially since the marketplace is still so new and people are still only beginning to learn how to interpret the results. “When you get these tests done, you sign a lot of pieces of paper that say you know what you’re walking into,” he says. “They even at one point in your waivers say, in caps, ‘You may find out things you don’t want to know.’” Knome founder George Church of Harvard Medical School says the U.S. Genetic Information Nondiscrimination Act of 2008 prevents insurance companies from upping their premiums or dropping consumers who discover bad things from genetic testing. However, he adds, the act “doesn’t stop consumers from gaming the system.” If a patient finds out her genome gives her a clean bill of health, she might cut back on insurance coverage—reducing the pool of money insurance companies use to pay for expensive care for sick subscribers. Or if a patient learns he’s at a high risk for something such as Lou Gehrig’s disease, he may preemptively sign up for all the medical coverage money can buy. Such scenarios ultimately aren’t fair to insurance companies, Church says. He suggests that the insurance industry now needs to team up with geneticists to brainstorm ways to work within GINA while still discouraging abuses of the system. While it’s common practice now, DNA evidence wasn’t used to convict or exonerate criminal suspects until 1986, when Richard Buckland was exonerated despite having confessed to rape and murder near Leicestershire, England. A year later, the first person was convicted in America on the basis of DNA evidence. According to the Innocence Project, more than 250 people in the U.S. have been exonerated through postconviction DNA testing since 1989. ictor McElheny, author of the new book (Basic Books), says some cancer patients today are already having parts of their genome—and sometimes a tumor’s genome—sequenced. “When you do cancer chemotherapy, you’re operating pretty much by guess and by God,” he says. “An awful lot of cancer drugs only help maybe one-third of the people who get them. … You’d like to know what the person’s own genetic predispositions are, so you can start picking the right drug the first time.” Cancer treatments are the first in a line of predicted “personalized medicine” breakthroughs, in which a person’s genetic information helps doctors tailor the treatment to the patient’s specific body chemistry. One big problem, however, is that well-trained doctors in genetics are still a rare breed today. And patients, more and more, will need good genetic advice. Matthew Bower, a genetic counselor at the University of Minnesota Medical Center in Minneapolis, says his field is entering an age of data overload. A’s, C’s, G’s and T’s can crowd out useful medical knowledge and counseling as much as it can help bring it on. “There are not enough genetics professionals to be managing everyone’s genome out there,” he says. And without good counseling, he says, people can still make bad decisions. For instance, Bower says he recently spoke to two journalists who had small parts of their genome sequenced and learned that they didn’t have one particular gene mutation that increases the risk of breast cancer. “They said, At least I don’t have to worry about breast cancer,’” Bower recalls. But breast cancer is caused by both environmental and genetic factors. And its genetic causes alone, he says, could come from dozens or hundreds of possible mutations in a person’s genome. “People tend to perceive genetic information as black-and-white, all-or-nothing,” he says. “So if they don’t have the Parkinson’s marker, then they’re not going to get Parkinson’s. That’s false. Or if they have the Parkinson’s marker, then they’re going to get Parkinson’s. That’s also false.” he likelihood for confusion as the personal genome marketplace heats up has recently inspired the federal government to act. In June, the U.S. Food and Drug Administration informed the top consumer genetic-sequencing companies in the country—such as Knome and Illumina—that the agency could soon be regulating the personal genome and consumer genetics marketplace. Regulation, says Church, could entwine companies in red tape and slow the market down. On the other hand, he adds, it may not hurt much. The FDA’s intervention could actually help the fledgling genome industry: “Reading about this in the news and seeing the FDA seal of approval,” he says, might also lead consumers to want to try out consumer genetic testing. Grant Campany, senior director of the Archon X-Prize for Genomics, says the FDA’s move itself constitutes a kind of endorsement. “The industry is going through a natural state of evolution,” he says. “It’s in everybody’s best interest that there’s a certain standard or benchmark—what quality really means.” FDA regulation of the marketplace also means that the June 2010 price tag for complete genome sequencing from the top two companies—Knome ($39,500, which includes genetic counseling) and Illumina ($19,500)—may soon be subject to change. Campany particularly has his eyes on the future of the marketplace, as he’s supervising the privately funded $10 million “X-Prize,” which will be awarded to the first company that can sequence 100 genomes in 10 days or less at no more than $10,000 per genome. Biotech journalist David Ewing Duncan says it’s still early, but at least a subset of the world is fascinated at the prospect of being the first generation in human history to read their own blueprint. In 2009, he published a book that traces his sometimes enlightening, sometimes-confounding experiences subjecting himself to genetic tests from companies such as 23andMe and deCODE. (Duncan hasn’t yet had his whole genome sequenced, however.) s conclusion, in short, is that a lot of genetic and genomic tests are scattershot: A little bit of information here, a little bit there and a lot of confusion elsewhere. Yet the field is progressing at great speed, too. It’s not just looking at individual DNA base-pairs, but also making sense of larger patterns within the genome—discovering, for instance, that one DNA base-pair may suggest that a person is good at digesting milk, but a larger grouping suggests he’s actually, on balance, lactose intolerant. “We’re a lot closer than I’d have thought. But it’s like a thousand points of light that need to be connected,” he says. “We took apart the human body. Now we have to put it back together.”