I posted previously on the decision by the US Court of Appeals for the Federal Circuit to uphold the patents on the genetics company Myriad’s gene sequences for breast cancer research and therapy. In September 2012 the American Civil Liberties Union once again petitioned for Supreme Court review. The Court should decide today whether to review the case.
The whole question of proprietary claims over genetic information is not limited to patents and is very much open to debate. In my piece on the US Bioethics Commission’s report to the Obama administration I discussed the challenge faced by lawmakers in regulating the increasing flow of genomic information so as to protect people’s privacy without shutting down the flow of data vital to biomedical research. Whilst it is true that the availability of patent protection creates vital incentives for such research, genetic testing companies like Myriad can extend their exclusivity beyond their patented products by creating limiting access to private databases containing information vital to interpreting the clinical significance of human genetic variations. There is concern that this threatens to impede the clinical interpretation of genomic medicine. The Genomics Law Report Journal reports that
National health systems and insurers, regulators, researchers, providers and patients all have a strong interest in ensuring broad access to information about the clinical significance of variants discovered through genetic testing.
The full article, which is open access, is in the European Journal of Human Genetics. In essence, the authors say that the Myriad patent saga serves as an excellent case study of the importance of collecting clinical data and the implications of keeping those data private. Myriad’s imminent entry into Europe presents an opportunity to implement policies on access to data on the mutation of the BRCA gene which leads to breast cancer. Such policies would set a salutary precedent not only for BRCA but for genetic testing in general, including whole-genome analysis. Mutations on single point mutations on active stretches of the gene are clearly deleterious because they disrupt protein function. Data on these mutations are valuable to those tested and to their health providers, influencing decisions about treatment options. But other data is being withheld, report the authors, which could be essential for further research in the analysis and treatment of cancer caused by single point variations. These are ‘variants of unknown significance’ (VUS). They occur between the active and inactive segments of the gene and are therefore particularly difficult to interpret. The paper reports that Myriad claims that the fraction of cases resulting in a VUS is 3% in its hands, and 20% for most EuropeanBRCA-testing services:
This discrepancy is at least in part due to Myriad having sole possession of the information needed to interpret VUS results. Myriad has obtained this exclusivity by using its status as the sole BRCA1/2 test provider to develop, at its own cost, an extensive database that relates variants of uncertain significance to phenotype, details their frequency in various populations and includes genetic studies on patient families. Thus, Myriad’s proprietary database that contains information about variants, which is not found in public databases, is probably the major factor in explaining the company’s ability to interpret VUS results more successfully than others.
As a result of this, the authors explain, there is an imbalance. Myriad has access to public databases in interpreting mutations, but outsiders do not have access to Myriad’s database. This asymmetry has clinical impact: a woman might be able to receive BRCA testing from another laboratory in Malawi or Malta, where Myriad’s BRCA patent rights are not in force and testing is perfectly legal, but that laboratory will have no access to Myriad’s data and will thus be unable to interpret many VUS results. Whilst it is inevitable that there are geographical inequities in the market for medical products and services – witness the long running HIV treatment litigation in South Africa – there should not be such inequity based on the availability of basic scientific and medical information. Such clinically relevant information should not be kept as a trade secret. In any event, such secrecy makes independent verification of its medical significance impossible. Myriad has, for example, published some information on the VUS results, but merely mentioning thousand- odd variants is not enough. Researchers need to know the underlying sequence of nucleotides so that they can replicate these genes in the laboratory themselves and interpret them. Whilst some may think that Myriads proprietary advantage in its (unpatented) pursuit of VUS cases are the just rewards for its innovation, there are others who, as the authors of the report point out,
are likely to consider the withholding of unpatented patient data to hinder rather than ‘to promote the progress of science and useful arts,’ the Constitutional mandate upon which the US patent system is founded
The report comes up with some solutions to this problem of enforcing openness of information. The medical journals should insist on full disclosure of the underlying data that is necessary to support the major claims of the paper and would enable others to verify or replicate the claims. Physicians receiving results, or the organizations that collectively represent them, could also demand access to clinically relevant data. On a higher level, national authorities that regulate genomic tests could mandate public disclosure as a condition of pre-market approval. If current practices of proprietary databases are allowed to continue, the report concludes, they may hinder interpretation of genomic data and impede the advance of personalized medicine.
Whole genome analysis stands poised to have a major impact on medical care if it can be harnessed appropriately. But the biggest challenge to its implementation is properly interpreting the variants found upon analyzing any individual’s genome. As whole-genome and whole-exome sequencing become commonplace, the rate of truly novel mutations will eventually decline. For the foreseeable future, however, each individual whose genome is sequenced will have vast numbers of variants of uncertain clinical significance
Myriad’s entry into Europe will force policy choices into stark relief, just as the reduced cost of full-genome analysis brings a worldwide deluge of genomic data.
- Can we keep our genomes quiet? Some suggestions from the US
- Can an individual claim ownership of life’s instructions?
- Can morality be explained by science?
- DNA, home testing and fuzzy human rights
- Should we outlaw genetic discrimination?
- What is genetic discrimination, and when and how can it be prevented?