Keeping It in the Family

Manuel Corpas

Reinhard Schneider

Not as many people around the world cared about the genes of Manuel Corpas and his family as he had hoped. As a result, after raising just one-fifth of the money he had aimed for, the 35-year-old bioinformatician of the Genome Analysis Centre in Norfolk, U.K., called an end last week to an effort to crowdsource funding to sequence his family’s DNA, an initiative Corpas says he launched to raise awareness of the coming personal genomics revolution.

Corpas's interest in the topic started as a hobby inspired by his work. Several years ago, he was helping to develop a database for patients with rare genetic diseases when he started wondering what his own genome might reveal. "I was constantly trying to understand the phenotypes of other people," he says, and thought, "why not try myself?" He bought a mail-order kit from the personal genomics company 23andMe, sent in a half-teaspoon of saliva from which the firm could obtain his DNA, and waited. No nasty surprises lurked in the half-million base pair sequences that 23andMe had analyzed, aside from a slightly elevated risk of prostate cancer. The bad news, for a scientist such as Corpas, was that his genes seemed rather dull.

Corpas was convinced, however, that more interesting information could be gleaned from his DNA. In order to compare his genome with his family's, he asked his mother, father, sister, and maternal aunt whether they would submit DNA to 23andMe and get 1 million genetic markers, known as SNPs, sequenced, and have their information made public. All agreed.

Corpas also has three kids, but he and his wife, who has no interest in having her genome sequenced, decided not to include them in the project. Corpas's eldest son has Down syndrome, and while Corpas says he's curious to see the child's genetic data from a scientific perspective, he would never make it public.

One reason Corpas was eager for the results of his other family members was that he was itching to use a computer program he'd co-developed, called myKaryoView, to compare the genomes. As part of his interest in "open" science, Corpas has made the tool and its software freely available for people to modify and improve.

After all of his family's genetic data provided by 23andMe had been analyzed, Corpas ended up publishing several reports in scientific journals, including a personal narrative of his family's experience with direct-to-consumer genetic testing and the results of his and his colleagues' attempts to interpret his family's genetic data using only free programs available on the Internet.

Encouraged by this limited family genomic analysis, Corpas decided to go further and fully sequence his family's exomes, the protein-coding portions of genomes. After negotiating with the massive DNA sequencing company BGI to do the exome analyses for $20,000, on 20 June he began a crowdfunding campaign to raise the money, promising to release his family's DNA information into the public domain and use the data to further develop public tools for people to analyze their own genomic sequences. Corpas posted a YouTube video that describes his project, explaining why he believes that openly sharing genetic data is important, and soliciting donations. Although wonderful technologies exist to analyze genetic markers and traits, he says, they are often not publicly available. "Anyone in the world who would like to know about their genetic data should have the resources to learn about it," he says. "My vision is about accessibility."

This week, however, Corpas ended the campaign, disclosing on his blog that he had raised only $3,526.59 from friends and family, which he will now use to sequence the exomes of his parents and sister. Although it is not as much money as he’d hoped, he writes in his blog, "Certainly this is a step ahead in our adventure to understand ourselves better."

Corpas's project has drawn a mixed response from colleagues and others exploring the personal genomics frontier. "Horror," for example, is how Darren Logan describes his initial reaction to Corpas's decision to publish his family's data. A geneticist at the Wellcome Trust Sanger Institute in Hinxton, U.K., who is somewhat of a mentor to Corpas, Logan works with only human genomes that have been encrypted several times to ensure their privacy. Openly shared genetic data is a raison d'être for scientists such as Personal Genome Project founder George Church and the largely Sanger-based geneticists who have published their own data through Genomes Unzipped, but Logan notes that sharing one's own information is different from sharing your family's information. And although he supports the project and recently co-authored one of Corpas's papers, he wasn't entirely convinced that Corpas had his family’s informed consent.

Corpas had followed the protocol for obtaining consent on 23andMe's Web site, but all that required, according to Anna Middleton, an ethics researcher and genetic counselor at the Sanger Institute, was checking a box for each family member through his own online account—no additional proof was needed.

What constitutes "informed consent" in the era of personal genomics is a matter of debate. Corpas says he questions the idea himself. None of his family members has a scientific background. Although he says he explained the genetic tests to his family as well as he could, he didn't have any training or knowledge of how to communicate the complexity of what genomic testing can and can't reveal. Although we understand a limited number of traits and disorders in which a gene is clearly involved, such as Down syndrome or the early-onset Alzheimer's, most depend on a range of complicated environmental and genetic factors that we understand poorly, contrary to what many direct-to-consumer genomics ads suggest. Even with a Ph.D. in bioinformatics and full knowledge of the limits of genomic interpretation, Corpas says he fell for the ads. "I wanted to 'empower prevention' and 'have a healthier future,'" he says.

When the SNP results arrived from 23andMe for the initial family analysis, Corpas says he realized that he had entered unfamiliar, uncomfortable, and emotional territory. Without really intending to, he says, he had become the "guardian" of his family's genetic information and the gatekeeper to potentially serious health information. Even as a scientist, Corpas acknowledges, he hadn't fully understood the potential emotional consequences of managing the 23andMe accounts for his family. "It hit me—how would I explain high-risk results to my mother?" referring to discovering a genetic marker that increases the chances of developing a disease. Only one such finding came up in the tests: His aunt has a high risk of the blood-clotting disorder venous thromboembolism.

Since 2003, when the first human genome was made public after a sequencing effort that took more than a decade and cost around $3 billion, the cost and speed of sequencing has halved yearly, making it feasible for anyone with a few thousand dollars to get a significant fraction of their genome sequenced. Based on his experience with 23andMe, Corpas foresees a tidal wave of genetic information about to engulf an unprepared public. The important thing, Corpas says, is to prepare for the moral quandaries and scientific challenges ahead by talking about the issues openly and developing open source tools to interpret the information so that it is not monopolized by private interests. He also believes that people should donate as much nonanonymous genetic data as possible into the public domain. To benefit from the discoveries made from the analysis of genetic data and not contribute one's own data to the field, he says, "could be seen as selfish."

Wylie Burke, a bioethicist at the University of Washington, Seattle, agrees with Corpas that the only way we'll ever gain a fuller understanding of how our genes affect our traits will be to gather massive amounts of genetic data from diverse populations and develop powerful computing tools to interpret and keep track of it. However, she suggests that focusing on making that data public will skew the collected data toward the population of the people willing to share—a biased sample—and compromise people's privacy in risky and unnecessary ways.

James Evans, a clinical geneticist at the University of North Carolina, Chapel Hill, applauds Corpas's desire to develop alternatives to the genome analysis tools used by private companies, but says his view of the future in which genetic data is shared as openly as compromising Facebook photos is highly unrealistic. People have valid concerns in protecting their privacy—particularly when it comes to disability or life insurance, for which no legal protection from genetic discrimination exists, he notes. There are also potentially serious public health consequences of an increased population of "worried well"—people who are outwardly healthy but scared into medical testing by genetic information suggesting they are sick or will become sick. "None of us pays for our own medical care," Evans says. "I have a vested interest in seeing that even if you pay for a test, that you don't use that information in ridiculous ways."

Corpas says his project was meant to spark these debates, not necessarily end them. "That's part of the fun," he says, "to speculate what could go right and what could go wrong." The issue of personal genomics, he says "touches every single one of us. We are used to an individualistic perspective of health care," but "personal genomics are going to change that completely."

Other personal genomic initiatives:

The Personal Genome Project:

Founded in 2007 by Harvard University scientist George Church, the Personal Genome Project aims to sequence the genomes of 100,000 volunteers, creating a database that matches each individual’s genome with personal information such as health and medical records. So far, they’ve sequenced nearly 2000 genomes.

Genomes Unzipped:

A collaboration between researchers in the field of genetics and legal and public health experts, Genomes Unzipped has released genetic data from its members to the public, as well as a custom genome browser and free software code. The project also discusses issues of genetic privacy and science through its blog.