The Burden of Knowing

For the right fee, a Cambridge firm called Knome will unravel all the secrets hiding in your genes. But what happens when those secrets include a higher risk of getting cancer? Or of contracting a crippling disease like Alzheimer’s? Would you be able to handle that information and the terrible choices it forces?
I wasn’t.

The following year, Harvard gave Church a second chance. There he started working under Nobel Prize–winning chemist Wally Gilbert, developing with him a new DNA-sequencing method, work that in turn led Church, at a meeting in 1984, to discuss ideas that ultimately became the Human Genome Project. But in the end, Church was disappointed that the 13-year, $2.7 billion undertaking chose to use existing technology to sequence one human genome. He all along had bigger goals in mind.

Before the Human Genome Project was completed in 2003, the scientists involved discovered that gene mutations—missing or repeated letters in the code of a gene—could be linked to certain diseases, and doctors began offering patients genetic tests for them. And yet apart from these mutations, most scientists didn’t know (and still don’t know) what most genes did. Put another way: They had come close to transcribing the entire book of life, but their proficiency in the language didn’t go much beyond “I seem to have lost my luggage” and “Where’s the bathroom?”

Church wanted to push toward fluency. In 2004, at his Harvard Medical School lab—the Center for Computational Genetics, one of the largest research labs in the Longwood Medical Area—Church began to design the Personal Genome Project. It would sequence a portion of the genomes of 100,000 volunteers, gather their medical records and note their personal traits, and make it all publicly available for scientists the world over in the hopes that they would make associations between genetic variations and health outcomes—that they would begin to fully understand what the “words” of the language of life really mean.

As Church talked about his project, he started to receive messages from people with a common request: They wanted Church to sequence them. Some had diseases in their families for which science had been unable to find a genetic cause. Others were potential investors in the field. All were extremely wealthy. But Church didn’t want to do such work in his academic lab, so he got together with a young biotech executive, Jorge Conde, with whom he had worked before, and serial entrepreneur Sundar Subramaniam. In November 2007 Knome was launched, offering complete sequencing at its original $350,000 price tag.

Today, by contrast, there are three other companies—deCodeme in Iceland and 23andme and Navigenics, both in California (and both backed by Google)—providing economy-class genome scans. They all use a cheaper technology to seek out single nucleotide polymorphisms, or SNPs (pronounced “snips”): genetic variants that have been statistically correlated with various traits and diseases. Customers pay as little as $400 to mail in a sample of their saliva. In about a month’s time, they can log in to their account on the company’s website and see whether they have, for instance, a 2 percent greater-than-average risk of getting diabetes, or a 20 percent lower chance of a heart attack.

The market for genomic analysis is still in its infancy, but by offering complete sequences, Knome has secured a reputation as the first-class player in the industry. The company says it met its target of landing 20 clients in its first year of operation. Knome’s customers receive hours of initial counseling and information on what science can and cannot tell them about the contents of their genome. Then, once a client has wired half the fee to Knome’s account, the company dispatches a physician to meet him or her—anywhere in the world—and collect four vials of blood. The DNA is extracted in New Jersey and sequenced in China. Back in Knome’s Kendall Square headquarters, a stable of bioinformaticians pore over the data and cross-reference it with the most up-to-date genetic research. Taking advantage of its Cambridge location, Knome often asks other local genetic researchers to discuss with the company a particular aspect of a client’s genome.

Then it’s showtime. The client is flown in, with his doctor if he chooses, to meet the company’s scientists (accompanied by Church himself when his schedule permits) for a daylong, one-of-a-kind, high-tech “me show” at Knome. The client takes home a binder, a few inches thick, with details about his or her genome and, of course, the flash drive with his or her sequence downloaded on it, to keep and cross-reference with every new genetic discovery.

For now, Knome and its genetic profiling counterparts remain privately held. No company will talk about its financials, and no in-depth analysis of this young industry exists. But Bruce Carlson, the publisher at Kalorama Information, a medical-market research firm, says there’s little doubt personal genomics will be a “very profitable” field. “The problem won’t be [lack of] customers,” he says.

That’s what Church is betting on. As he and other scientists improve the technology, which will in turn lower the price of complete sequencing to $1,000, he hopes that everyone will want the service. Of course, Church assumes that the expense of sequencing is the big obstacle to his vision becoming reality.


  • Jack

    Get in touch with me. I have thought of you often over these years, wondering if you still want bagels.