新托福阅读材料汇总：Genome Sequencing for the Rest of Us

We all carry our DNA around with us—in every cell of our bodies—but some biotech trailblazers are toting their genomes with them, too. In a recent talk Jay Flatley, president and CEO of sequencing giant Illumina, recalled being asked by his doctor to get a certain genetic test. But Flatley was able to pull up his full genome on his iPad then and there instead of sending a spit sample off to the lab.

Although most people are not yet able—or willing—to obtain or share their own personal genome sequence, many already see a genome-empowered future dawning. In the quest to better know one's self, however, more and more people are turning to genome sequencing to uncover information about their ancestral histories, impending health risks, and disorders of potential progeny. After the U.S. Food and Drug Administration (FDA) prevented Pathway Genomics' direct-to-consumer DNA kits from reaching drugstore shelves in May, however, the technology—and companies who offer it—have come under finer scrutiny from the public as well as the government.

Despite the completion of the generalized human genome draft a decade ago, connections between diseases and genetic variations have proved to be evermore complex and elusive.

"We naively thought that there would be a few genes involved in risks for a variety of common disorders," says Barbara Bernhardt, an associate professor of medicine and genetic counselor at the Hospital of the University of Pennsylvania (Penn).

Some conditions, such as cystic fibrosis (pinpointed even before the completion of the human genome), are caused by single gene mutations, and clinical genetic tests for these types of diseases have been useful diagnostic tools. But other diseases, such as Alzheimer's, have no uniform genetic signature—or clear way of avoiding them—leaving many to wonder about the science and utility behind the results many genome scans offer casual consumers. Other information gleaned from sequences—for example, the drug metabolic-rate estimates for medications such as the blood-thinner Warfarin—could be used directly for medical treatment decisions.

"They certainly do provide medical information to people," Bernhardt says of the direct-to-consumer genomic tests. "From that perspective, they do need to be regulated as medical devices."

The FDA, which had provided relatively loose rules for consumer genetic testing, is now revaluating the industry's methods and will begin asking companies to provide data about how they interpret the scans for customers.

In a 2006 Scientific American article, Harvard Medical School geneticist George Church called for genome sequencing for all. But four years later, is the technology ready for the mass market?

Testing the market

The first complete individual human genome was finished less than three years ago and cost hundreds of millions of dollars. Now many companies offer a similar service, which promises a personalized laundry list of disease risks assessed from a simple cheek swipe or spit test, available online for thousands—and in some cases, for less complete scans, hundreds—of dollars.

Despite the drastic decline in price and increase in availability, direct-to-consumer genome sequencing has been relatively slow to catch on. The Google-backed sequencing company 23andMe has gone through two rounds of staff cuts in the past several months, and the Iceland-based deCODE genetics was delisted from public trading on Nasdaq earlier this year after its market value dropped.

Additionally, a mishap earlier this month at a lab under contract with 23andMe resulted in as many as 96 customers receiving the wrong genetic reports.

"The consumer market for whole genome sequencing and interpretation has yet to evolve," says Nathan Pearson, director of research at Knome, a company that offers full genome sequencing. Recent studies have also found other applications for genetic tests, such as ancestry profiles, to be rather unreliable. And many consumers are reluctant to submit their DNA for private sequencing—let alone inclusion in genetic studies—fearing privacy issues.

Even so, research shows that genetic insight into health risks is in high demand in some consumer groups. In an ongoing study of attitudes toward genetic testing at Penn's School of Medicine, Bernhardt and her colleagues have found that their subjects generally embraced and understood their genetic test results and risk levels. Their volunteers were primarily people who took an active interest in their health, she notes, and results were presented only for a single condition for which preventive actions could be taken (such as risk for heart disease), rather than a fuller scan of multiple risks that many of the direct-to-consumer tests offer.

But for conditions in which there is currently no cure or effective prevention there is concern that just downloading a personal genetic risk profile at home might cause undue stress or even depression. Bernhardt and others recommend that consumers meet with a genetic counselor before tests to prepare for what information might come back—and for how it should be used.

The family doctor, however, might not be ready to help in interpreting genetic test results. Bernhardt notes that a lot of general practitioners often do not know what to do with this genetic information.

Recoding the code

Even for genetic tests that offer just a snapshot of relatively common disease-linked variations, the amount of data such a scan generates is immense and requires distillation before relevant information can be presented to consumers. This process of interpretation, however, is one place where the science can get murky.

Most companies offer genetic data in terms of relative risk for particular conditions. Some, including Knome, provide links to scientific studies about genetic variants that appear in your genome, allowing a customer to judge what a particular difference might mean for them. Their personal scans, however, have primarily been limited to a few dozen "healthy and wealthy" customers who are motivated to dive into the literature and explore health implications for themselves.

"Dealing with the huge haystack of data that you get is a really difficult task," Pearson says. And that service is not likely to disappear, even as sequencing prices drop. "When sequencing is free or nearly free, there will always be room for expert interpretation," he says. "That's our stock and trade," he says of his work with Knome.

That approach could have limitations for much of the public who might not be interested in sifting through a decade of scientific literature about a particular mutation they carry. "They're going to get overwhelmed," Pearson notes about consumers who get inundated with mountains of data about their 3.3-billion base-pair genome. Finding ways to convey results "judiciously, securely and wisely" will be a long-term challenge for the industry, Pearson says.

No magic markers

Another challenge to consumer genetic testing has been consistency. Although most sequencing processes are similar, and the DNA itself is a unique code, reports from various groups for a single person can have striking differences. "People interpret the information that comes out of the sequence differently," notes John Boyce, co-founder of Delphi Bio, a biotech consulting firm, who also founded the annual Consumer Genetics Conference.