Barbara Zeughauser had lost so many relatives to cancer: Her mother, her uncle, her grandmother, her second cousin. She thought that ghost in the family line might come after her, too. So in 2009, Zeughauser took a test offered by Myriad Genetics. It analyzed her DNA for mutations in the BRCA1 and BRCA2 genes that can make cancer more likely than not, raising the lifetime risk of breast cancer in women to between 55 and 85 percent, and to between 10 and 70 percent for ovarian cancer.

Zeughauser was lucky and unlucky. She got a clear, unambiguous, and accurate answer from the test: She had a bad mutation. But she’d found it before she got cancer. She decided to have her ovaries removed and later had a double mastectomy, reducing her risk to almost average.

Her cousin Ken Deutsch wasn’t so lucky. In 2014, he was hit with bladder cancer. He also went to Myriad and learned he had the same genetic glitch.

Deutsch wanted to know more detailed information about this mutation, because it might shape his decisions about treatment, his thoughts about his own future, and the risk for the rest of his relatives. So he Googled. He Facebooked. He searched ClinVar, the federally hosted scientific database with hundreds of thousands of examples of inherited gene mutations and their likely consequences. It included only three other examples of people with this mutation and not much information about what it had meant for them.

He was surprised there was so little information out there, but he soon found out why—and learned that the reasons have more to do with money than with medicine. Even though DNA data can be the key to understanding or even successfully treating cancer, some of that potentially life-saving information isn’t publicly available. Myriad, for instance, claims that releasing it creates a privacy risk. Other data languishes in the databases of testing companies and medical center labs, simply because sharing it is technically difficult and expensive.

The realization would turn Deutsch and Zeughauser into activists—two ordinary people determined to make sure genetic data gets shared for the benefit of all.

 

Interpreting a BRCA mutation is an art. There are more than 19,000 different known mutations in the two genes. Most are harmless, a few almost guarantee cancer, and others are somewhere in between. To figure out which are which, companies like Myriad analyze a person’s DNA, then interpret the sequence by consulting medical studies, computer models, expert committees, and databases that include other examples of the same mutation.

Myriad has built its own such database, and it is the biggest and the best, because for about 15 years, the company had a patent on the BRCA genes, preventing any other US lab from offering the test. Over the years, the company built up a massive reservoir of information, millions of data points linking different mutations to their consequences for cancer risk—all private.

The American Civil Liberties Union (ACLU) and the Public Patent Foundation filed a lawsuit in 2009 claiming that Myriad’s patent violated the law, and in 2013, the Supreme Court agreed, breaking the company’s legal monopoly. Almost overnight, other companies starting offering the test. But Myriad’s database, the single best source of data about the connection between BRCA mutations and breast cancer, remains a trade secret to this day.

There’s no law against it. But many think it’s an ethical outrage. If other companies or nonprofit labs could also look up gene mutations in that database, it would help all patients—not just paying Myriad customers—get better answers and more information. “My strong feeling is that the sequestering of this information for proprietary purposes is wrong,” says cancer geneticist James P. Evans of the University of North Carolina School of Medicine. “It’s counterproductive for patients, for the medical endeavor broadly, and for society.”

Genetic medicine is a game of numbers. The more examples you have, the better your interpretations get. So because they couldn’t get access to Myriad’s database, many other genetic testing labs—companies like Ambry Genetics, GeneDx, and Invitae, as well as large academic medical center labs—pledged to share their data. To share, they remove personally identifying information like names from genetic tests and submit the results to the public ClinVar database so that all test providers, including their competitors, can access the same information.

Myriad stopped contributing data to public repositories in 2004. The company says data sharing can be a privacy risk. “We believe that the patient alone has the right to decide if their own genetic information is shared publicly,” says Myriad Chief Medical Officer Johnathan Lancaster in a company video.

It is sometimes possible to identify people who have anonymously donated extensive amounts of DNA sequence data to a public database or genealogy website—for example, that’s how investigators narrowed down their search for the Golden State Killer. But so far, there are no known cases of people being identified through an anonymized breast cancer test, because it zeroes in on just a few of the roughly 20,000 human genes. One expert in DNA reidentification calls the claim “nonsensical.”

Myriad spokesman Ron Rogers suggests that one problem with public databases is that patients like Deutsch don’t always realize their genetic information is being shared. The company also says public databases are riddled with errors. In April 2017, a study sponsored by Myriad reported that nearly 27 percent of the mutation interpretations in ClinVar differed from Myriad’s own interpretations and were, in the company’s view, limited or wrong.

However, that study used ClinVar data from 2015, and the database’s quality and quantity have steadily improved since then, says Heidi Rehm, associate professor of pathology at Harvard Medical School and chair of the federally funded group that works with ClinVar. The paper takes “a completely naive and uninformed approach,” charges geneticist Robert Nussbaum, chief medical officer of rival gene testing company Invitae.

But even if ClinVar is improving quickly, it still might not have every one of the rare variants in Myriad’s database. To accelerate that process, several grassroots projects launched crowdsourcing appeals, calling upon patients and doctors to get their own data from Myriad and deposit it in public databases.

 

At the end of 2015, Ken Deutsch learned that the ACLU was looking for volunteers to request all their data from Myriad—which is their right under the Health Insurance Portability and Accountability Act (HIPAA). Deutsch signed on. “I’m an activist in my blood,” he says.  “If we can get everyone’s data, then we can get more answers sooner.” Zeughauser and two others also joined in.

He and three others eventually did get some additional data back from Myriad, but in its correspondence, the company said it was doing so per Deutsch’s request, not as the result of a change in policy. So on May 19, 2016, the ACLU filed an official complaint with the Department of Health and Human Services (HHS) Office for Civil Rights, which enforces HIPAA’s privacy and security rules. They want to force Myriad to release more complete data records—including information about how gene variants are interpreted—routinely to anyone who gets tested with the company and requests their information. “We receive hundreds of patient requests for information about their tests every year and routinely satisfy those requests in an appropriate format,” responds Rogers.

More than two years later, HHS has made no public response and refuses to answer any questions about the status of any investigation. It’s a stalemate.

In the meantime, as ClinVar steadily grows, extracting data from Myriad gradually becomes less important for other test providers, and the value of the company’s proprietary database slowly shrinks. It may be that before HHS ever makes a move, the BRCA fight becomes a moot point. When the current version of Myriad’s test was launched in 2014, the list price was between $4,000 and $4,500, although insurance often pays part of the cost, and the company offers financial assistance to some patients. In the last few years, companies like Color Genomics and, most recently, 23andMe began offering hereditary cancer tests for as little as $99. (Each is different, but 23andMe’s test covers just a handful of the most common gene variants and wouldn’t catch a mutation like Deutsch’s.)*

At the same time, international cooperative efforts like BRCAExchange, which pools test results from around the world and from Native Americans in the United States, are adding new diversity to public databases—a range of genetic variation that Myriad’s databases might not match.

Genetic data sharing is only going to become more crucial. Researchers now understand there are other inherited gene mutations like BRCA out there that greatly increase the risk of other types of cancer—but which mutations and by how much is still unclear. That problem can only be cracked through cooperation. “The only way that we’re going to learn how to interpret genomic results is through broad sharing,” says Evans.

Even though many companies and labs have promised to share, they don’t always follow through. The pioneering genetics department at Baylor College of Medicine co-owns a for-profit lab, Baylor Genetics, which has contributed only a small number of variants to ClinVar (650 results total, and only 146 for BRCA). Baylor Genetics Chief Scientific Officer Shashikant Kulkarni says the lab is committed to data sharing and has, in fact, contributed 90 percent of its recent BRCA test data. But since some other genetic test results date back almost 40 years, the lab has a major backlog. “This is not an excuse, but it is extremely cumbersome,” he says. “The technology is challenging, and there is no financial support.” Another prominent academic lab, ARUP Laboratories, is submitting just one batch of test results a year and none from before 2016. The lab does not have the resources to reanalyze all the older test results so they meet today’s standards, says Elaine Lyon, medical director of molecular genetics and genomics at ARUP: “In principle, we’re trying to share. In practice, we’re a little bit delayed.”

Preparing and submitting data to a public resource takes time and money and doesn’t give any one lab a competitive edge. With no incentive to share, data-sharing may fall by the wayside, since anybody can use the ClinVar database, whether they contribute or not. “Reciprocity hasn’t been built into the system,” says Robert Cook-Deegan, a genomics expert and professor in the School for the Future of Innovation in Society at Arizona State University.

The upshot is that even if the ACLU prevails, the broader problem may not be resolved until the system is set up to encourage, or even force, gene testing labs to cooperate. And that means that despite Deutsch’s activism, the Ken Deutsches of the future may still struggle to get the potentially life-saving information they want. “I’d like to see that every single person who is tested by any lab has the ability to request data, get it in machine-readable format, and upload it to other places doing the research,” he says. “Maybe with thousands of records, they could find something.”

Correction: This sentence has been changed to accurately describe which companies’ tests would have caught Deutsch’s mutation.