An effort to extend the time between the recently learned and soon forgotten
Myriad Genetics has been at the center of an ongoing tug-of-war between private profits and the public good for almost 20 years. At issue has been the question of whether corporations can restrict access to genes through patent law, or whether the information in DNA cannot be thus controlled. In June 2013 the Supreme Court of the United States invalidated Myriad Genetics' patents over the human genes BRCA 1 and 2, but Myriads’ attempts to mmonopolize breast cancer ggenetics still continues.
The story began in 1991 when scientists led by Mary-Claire King at UC Berkeley identified a tumor suppressor gene on chromosome 17. This gene normally helps to protect people with DNA damage, either by repairing the damage or else triggering cell death if the damage is overly severe. The mutated form of the gene is incapable of plying its protective role, however,lleading to an increased risk for both breast and ovarian cancer. This gene was eventually named BRCA1 (standing for Breast Cancer, early-onset), and, along with the related gene BRCA2, may explain roughly 10% of all breast cancers. A diagnostic test identifying the mutated form of either gene would therefore provide critically important medical information.
The importance of genetic testing was not lost on the business community, and in 1991 Myriad Genetics was incorporated in order to explore topics related to genomic medicine. By 1993 BRCA1 had been cloned and in 1996 Myriad launched their diagnostic kit. Not content to be one of many players in this rapidly growing field, Myriad moved to obtain patents over both BRCA1 and BRCA2. While the laboratory of Myriad genetics founder Mark Skolnick at the University of Utah performed important early research, pioneering scientific work was also done elsewhere, and that the majority of the work across all institutions was publicly funded. In the late 1990s genomic data in quantity was an unfamiliar commodity, so it’s hardly surprising that the patent office was ill-equipped to determine the scientific merits of Myriad's patent applications, let alone the larger issue of whether genetic material was suitable for patenting.
For years after Myriad's BRCA patent filings no woman could legally be tested to determine whether or not she was a carrier of mutated BRCA1/2 unless her doctors used the test sold by Myriad Genetics. If aa patient lacked the money for Myriad's pricey test or else wanted a second opinion then she was out of luck. Furthermore other scientists were prohibited from developing new tests, with Myriad aggressively bringing suit against anyone else seeking to investigate the genes that Myriad corporate officers wanted to control.
Thus while our scientific understanding of DNA and molecular biology advanced rapidly over the next 15 years, Myriad wielded its 23 patents in a litigious fervor that restricted all scientific and medical access to BRCA1 and 2. Eventually, however, the Association for Molecular Pathology, joined by the ACLU, challenged Myriad’s patents in court. An escalating series of verdicts eventually led to the Supreme Court, where in June 2013 the court ruled that Myriad’s patents were invalid. Myriad tried again by pushing forward with another series of patent claims, but on December 17 the Federal Court of Appeals rejected Myriad’s attempt to an alternative set of patent-based arguments. While the legal case might seem to be settled, Myriad’s sorry influence continues to negatively impact women’s attempt to learn about their cancer risk.
At issue is the information about specific mutations that underlie dysfunction in the two BRCA gene sequences. BRCA1 is over 80,000 bases long, after all, and there are many ways in which such a sequence can become dysfunctional (BRCA2 is shorter but still lengthy). During those years in which Myriad offered the sole diagnostic test they were able to accumulate information from each woman who used their test, and associating specific mutations with outcomes the bottom linein this sort of clinical work. While other researchers could now legally explore this region of the human genome, nobody else had had such a comprehensive database of specific mutations (known as 'variants'), and Myriad was unwilling to share their data. Myriad's claim became that while you, the patient, were indeed entitled to use someone else’s kit, you’d nevertheless be a fool to do it since Myriad had the best data and always would. Their plan was to protect their profits by maintaining this information as a trade secret, so that frightened patients would still have no other option than to purchase their diagnostic kits.
Around this time David Altshuler and 13 other leading geneticists from around the world started an organization which would eventually be named the Global Alliance for Genomics and Health. This non-profit group focused on disseminating genomic information, and developing interoperable standards intended make the information in DNA into a public resource. The Global Alliance brought academics and scientists to create a project called the BRCA Challenge. The BRCA Challenge is currently attempting to develop a catalog of all known variants in the BRCA genes, and linking these variants to clinical courses, medication regimens, and eventual outcomes. If the project succeeds then all women at risk for breast or ovarian cancer attributable to BRCA mutations will have access to the best care that science allows, rather than only the science that furthers Myriad Genetics' financial goals.
Many challenges still exist. Myriad is unwilling to systematically share their variant database, and scientists affiliated with the BRCA challenge have been asking former patients to fax in the paper reports they had received from Myriad. The de-identified reports are then transcribed into an electronic format but the goal of creating a public resource. While the size of the variant database thus acquired is increasing, it likely does not match the proprietary database still guarded by Myriad (though the exact size of their database is a protected secret, so we don't know for sure). If you'd like to know more, here is a video providing a status update of the BRCA challenge. You can also go to the Global Alliance website and explore some of the other excellent initiatives they are currently undertaking. This is a time of rapid change and grand possibilities in the world of genomic information, and one in which corporate profits sometimes need to take a backseat to the public good.
Chromothripsis (from the Greek for 'chromosome shattering') is a strange phenomenon normally associated with cancer. Chromothripsis results in a fundamental reordering of the DNA within a particular region of the chromosome, presumably leading to the activation/deactivation of many parts of the affected genetic code. Since this condition is observed in patients with cancer is usually considered to be a consequence of a pathological DNA replication, though chromothripsis may also cause or worsen certain types of cancer. In any case the event seemed inevitably to be bad news, UNTIL this recent news story. In this case on woman with a rare congenital defect appears to have been cured when a chromothripsis event occurred in one of her blood stem cells, rearranging her DNA so as to remove the mutated CXCR4 gene that was the cause of her troubles. The resulting healthy stem cell then replicated, leading to a predominance of white blood cells lacking the deleterious mutation. As a result the woman appears to no longer have the syndrome that had troubled her throughout her life (though her two sons continue to be afflicted). This surprising case suggests that the poorly understood phenomenon of chromothripsis may have some utility, representing the body's attempt to deal itself a new genetic hand in the face of severe illness. This is all breaking news -- further analysis from scientists and the area is ongoing.