The Year of Miracles

As of September, deCODE has made progress in identifying SNPs that may play a role in 28 common diseases, including glaucoma, schizophrenia, diabetes, heart disease, prostate cancer, hypertension and stroke. In some cases, such as glaucoma and prostate cancer, deCODE's findings could lead to diagnostic tests for identifying people at risk of developing the disease. In other instances, such as schizophrenia, links to particular proteins have led to insight about the cause of the disease, which could lead to therapies.

Buoyed by Stefansson's success, other geneticists were eager to perform large-scale family studies, yet few had similar access to ancient genealogical records. But serendipity would deliver an epiphany: it's possible to study the entire human population as a single extended family, provided scientists collect enormous amounts of data. Eric Lander, an MIT professor and the intellectual leader of the U.S. government effort to sequence the first human genome, realized scaling up would require a new approach. In 2004, Lander persuaded MIT and Harvard to combine their enormous resources toward the creation of the Broad Institute. Backed by $200 million from billionaire philanthropists Eli and Edythe Broad, the institute is driving the development of ever more advanced genetic technologies. One technology, based on computer-chip fabrication, can identify DNA base letters present at 500,000 SNPs in the genomes of 40,000 or more people.

Think of this as a spreadsheet with 500,000 columns (each representing a specific SNP) and 40,000 rows (one for each person). To hunt for a genetic basis for, say, bipolar disease, the computer searches rows of people who have the disorder, checking column by column for an unusually high frequency of particular letters in comparison with people without the disease. As it turns out, a collaboration of American and German researchers has done this work—and found that variations of DNA letters in 20 different positions are influential in bipolar disease.

Incredibly, most disease-causing variants are the most common ones present in the human population: the strongest-acting one, for instance, exists in 80 percent of people without bipolar disease and 85 percent of people with the disease. The implication is that these variants are beneficial in some way, and cause problems only when their number exceeds a threshold.

To make sense of this complexity, scientists would like ultimately to build a vast international database that contains the complete sequence of DNA bases in the genomes of hundreds of millions of people. Ideally, such a database would be available for analysis by all biomedical researchers and would provide the foundation for understanding the genetic components of all human traits. That sounds like a lot of data—think of a spreadsheet with 3 billion columns and 100 million rows—but computing power is getting cheaper by the year. Within a decade, the cost of obtaining a sequence of all 3 billion DNA letters in an individual's genome will drop from $2 million now to $1,000. It will be a routine part of a person's health record, enabling physicians to prescribe genome-specific preventions and treatments.

The discovery of RNAi, meanwhile, suggests a completely new personalized form of disease therapy. Whereas drugs act on proteins, RNAi therapy would act on the expression of DNA itself, potentially preventing or reversing diseases such as Alzheimer's, Parkinson's, Huntington's, bipolar disorder, schizophrenia and others. Old-school pharmaceutical firms have taken notice. The largest ones are betting heavily on the gene-targeted RNAi therapeutic approach to fill product pipelines, as the discovery of traditional chemical drugs becomes more elusive. Novartis and Roche have both signed nonexclusive licensing deals with the biotech firm Alnylam (founded by Phillip Sharp) for new therapeutic techniques that are valued at up to $700 million and $1 billion respectively; Merck paid $1.1 billion to buy another biotech company outright, solely to obtain its contested portfolio of RNAi intellectual property, and the London-based drug firm AstraZeneca has a $405 million licensing deal with Alnylam's competitor Silence Therapeutics.