Myriad Genetics, breast cancer mutations, and you.

by Chris Gunter  

Geneticists everywhere celebrated yesterday as the US Supreme Court issued its ruling in the case of “Association for Molecular Pathology v. Myriad Genetics, No. 12-398.” Here’s why you should celebrate too.

Myriad Genetics, a company based in Salt Lake City, has held a patent on two important genes in the human genome, BRCA1 and BRCA2. Many people believe that no one should be allowed to patent a gene because the vast majority of people have the same genes and thus no one should “own” them. However, studies have suggested that 20% of the genes in the human genome have been claimed as intellectual property. The unanimous ruling just issued by the Court actually said that isolated DNA or the human genome cannot be patented (as it is a “product of nature”), but that when human/laboratory intervention makes products based on the human genome, those can still be patented. [For a synopsis with more detail, see SCOTUSblog’s op-ed].

Turns out that Myriad owns 24 patents, both on the BRCA1 and BRCA2 genes themselves and on artificial sequences generated from them, called complementary DNAs or cDNAs. Most genes in the genome have short stretches of information, called exons, that serve as the code the cell uses to build proteins. Interspersed in between the exons and still part of the gene are long stretches of information called introns, which the cell does not use as code for proteins. In fact, when cells copy DNA into RNA to kick off protein building, the cell cuts those introns out of the RNA, leaving only the exons. We can use that cleaned-up RNA to synthesize a DNA sequence with only the exon information and no intron sequences. DNA made this way is called cDNA. (It’s “complementary” to the RNA molecule that was used as a template to make it.)

Labs make cDNA for a couple of reasons: (1) Without all that noncoding intron information in there, cDNAs are often much shorter than the original genes but still contain almost all of the important coding information for making a protein; and (2) DNA is more stable than RNA and can be used more easily in the lab for other purposes, like developing tests to look for mutations.

Back to the ruling: The furor in this case has been unique because it’s more about what Myriad did with their patents, which was to develop a test that sequenced through the two genes and then aggressively prevent anyone else from doing the same. Since 1994, Myriad has either bought out or used litigation to fend off any other company wanting to offer BRCA1 or BRCA2 mutation testing, giving themselves a monopoly and complete pricing power. This tactic has generated so much outrage that one of the plaintiffs in the case is the American Civil Liberties Union, claiming that the patents violate free speech by restraining scientific research.

Because any number of mutations in the BRCA1 or 2 genes can result in an inactivated protein and increased risk for breast cancer, the gold standard for determining mutation status is to sequence through the entire gene, instead of testing only for specific mutations in parts of it. Myriad’s BRACAnalysis test uses older technologies known as PCR and Sanger sequencing, and they used their monopoly status to charge a high price of $3000 or more for the test. In the last five years, newer sequencing technologies have emerged that allow you to get your entire genome sequenced for almost the same price. That includes all 20,000+ genes in your genome, not just 2.

Multiple sources have reported that they could use newer sequencing technologies to perform BRCA1/2 sequencing for $1000 or less. In fact, within hours of the ruling, companies announced that they would offer tests at that price. Most of us don’t have the salary of the lovely and courageous Angelina Jolie, who just announced her own decision to have testing and then have a prophylactic mastectomy based on a positive result for a mutation in BRCA1, so that $2000 difference is a big deal.

Many women like Jolie have been helped by tests like Myriad’s, allowing them to learn mutation status and make life choices accordingly. But the monopoly and resulting high cost of the test have been damaging for many families, given that many health insurance companies would cover the test only under certain conditions. The recent documentary “In The Family” deals with issues like these, and has a nice website with more information. The featured family did not go through Myriad but instead went to an academic center, in this case the lab of Dr. Mary-Claire King, whose lab helped discover the two genes [earning her a portrayal by actress Helen Hunt in a 2013 film called Decoding Annie Parker. We could have a separate column about when actors play scientists, but that will be another time. Julia Roberts for me, please.].

As expected, Myriad claims they won a victory because some of their patents were upheld, and the main patent in contention was set to expire in two years anyway. Scientists, physicians, patients, and advocates feel they won a victory (even if the scientific understanding in the opinion seemed to be shaky) because the door is now open for competition on pricing and quality of BRCA1/2 genetic testing. This ruling of course also sets precedent for other, similar debates on patents of other genes in our future, but few have the widespread reach and emotional battle surrounding them that the BRCA genes have. So, please, take a moment to celebrate along with us DNA geeks.

[Image credits: Mammogram image by U.S. Navy photo by Mass Communication Specialist 2nd Class Joseph Moon, public domain, via Wikimedia Commons. Supreme Court image on front page by Jeff Kubina, own work, public domain, via Wikimedia Commons. Image of Supreme Court, this page, CC-BY-SA-3.0/Matt H. Wade at Wikipedia. RNA splicing image, public domain via Wikimedia Commons. Image of Angelina Jolie, credit to Gage Skidmore, Creative Commons Attribution Share-Alike License.]