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.

knome

The author, a cancer survivor and mother of two. (photograph by tim llewellyn)

The flash drive comes in a silver box, sunken into a bed of black velvet, shining out, fittingly, like a rare gem. Fail 10 times to provide the correct password and the drive will self-destruct. The entire sequence of its new owner’s genome is inside this piece of brushed steel, all of his or her DNA. The Cambridge-based company selling the drive, Knome, is the only company in the world to offer anything like it. Only a handful of people in the world have one. For now.

The man responsible for Knome and the services it offers—services that will fundamentally alter the way we think about healthcare—is George Church, a 6-foot-5, bushy-bearded Harvard Medical School professor and the patriarch of personal genomics. His coming movement will wrest the genome from research labs and place it in the hands of the people, much as computers went from government and academia to being an inextricable part of daily life. The newer and faster technologies Church and his ilk are developing have already dropped what Knome charges for sequencing from $350,000 to $100,000. Church’s ultimate goal is to get the price down to $1,000, a price accessible for nearly everyone. When it reaches that point, he predicts, the genomic revolution will usher in an age of personalized medicine, in which doctors tailor treatments to a patient’s genetic makeup, to the individual strips of code that can serve as a marker for future diseases. It will allow patients an opportunity to truly—as the Knome motto goes—”Know thyself.”

Not everyone is greeting the revolution with outstretched arms. A chorus of doctors, ethicists, and even some of Church’s fellow geneticists say that personal genomics is a wildly unregulated and woefully immature field, one in which science’s ability to read genes, and Madison Avenue’s ability to hawk its tests, is eons ahead of medicine’s understanding of the results. When doctors do understand them, there is often no preventive measure consumers can take to head off their fate, if that fate is a disease like Alzheimer’s or Huntington’s. There’s also the fear that personal genomics may not only one day customize medicine to our genes, but also custom-design our children. The question for people who oppose Church is whether this world of his is any place for the rest of us.

 

George Church found his calling as a 19-year-old college student at Duke University. He was working in a lab, playing around with a program used to make three-dimensional models of RNA molecules. This was in 1974, when computers could do little more than show a 3-D image. He decided to type in thousands of RNA bases, which direct the function of the RNA molecule. These bases are encoded by the A, C, T, or G proteins that make up the rungs of one’s DNA. It took hours for him to type in the sequences before the machine spit back an image, which looked like strings of beads that folded back on themselves and then up until they resembled “little statuettes,” Church says. The connection between the linear sequence of DNA and the encoded shape and form it took on the screen was an epiphany for him. He pictured an age in which computers could map the whole of each person’s genomic sequence and translate it into his or her physical traits. Church vowed that day to spend his life bending the revelatory power of microprocessors to his will.

The moment set him on a career track that combined two of his childhood passions: biology and technology. As a boy Church had passed a lot of time alone, trapping and studying bugs from the ponds of his Florida island home and building basic computers from kits and spare parts. Something far less idyllic, seldom discussed but originating, too, in his boyhood, steered his early work as well. Church’s father walked out on him and his mother when Church was a few months old, taking with him Church’s sense of identity. “Because my first father left me when I was so young, I was never really quite sure who I was,” he says. “And I had this feeling that people in general didn’t know who they were, even if they lived in a nice nuclear family with all their grandparents nearby.” The genome became to Church “this big missing thing,” without which no one could truly understand himself. (Today, though the official pronunciation of his company is “nome,” Church insists on mispronouncing it as “know-me.”)

The quest to find this missing piece explains Church’s impatience. He wrapped up his undergraduate degree from Duke in two years. He began his research-heavy graduate work there immediately and soon was spending 100 hours a week in the lab. He skipped classes, missed exams. And flunked courses. In 1976 he was expelled.

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.

knome

George Church, the patriarch of personal genomics, believes that the truth of our genes, however awful, will also set us free. (Photograph by tim llewellyn)

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.

ADVERTISEMENT

  • Jack

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