Tuesday, December 18, 2012

Should Human Genes Be Patented?


Recently, there has been much controversy regarding whether it is legal for human genes to be patented; although genes have been patented in the past (~20% of all human genes have been patented over the past 30 years), the case regarding the patenting of BRCA1 and BRCA2 genes by Myriad Genetics has resulted in a landmark opportunity for the Supreme Court to rule on whether any patent on any human gene is legal. The Yale Student Science Diplomats discussed this case, now known as Association of Molecular Pathology (AMP) v. U.S. Patent and Trademark Office (USPTO), and its potential implications with Prof. Daniel Kevles of the History Department and the Law School. The discussion was titled, “Human Genes and Human Rights.”
During the discussion, Prof. Kevles provided the Diplomats with a detailed history of gene patenting, as well as the specifics of the case against BRCA1/2. These genes have been linked to hereditary breast and ovarian cancer, in which up to 8% of women with breast or ovarian cancer have mutations in BRCA1/2. The story began in 1990 when Mary Claire King located the BRCA1 gene on chromosome 17. A race quickly ensued to discover the exact location of the gene, which Myriad Genetics won in 1994 and again in 1995 for BRCA2. Myriad applied for 7 patents for these 2 genes in 1997 and 1998 and received them in 2001. Just a few weeks ago, the Supreme Court accepted claims against these patents for review. However, the legal history of this case dates back to 2009, when the American Civil Liberties Union (ACLU) and the Public Patent Foundation filed a brief against the USPTO and Myriad Genetics. This was the ACLU’s first patent case, and it drew enormous interest by various groups: the plaintiffs were the patients, physicians and medical researchers who claimed to be disadvantaged by these patents, and the defendants were biotech and trade associations who claimed that the patents were necessary to stimulate progress in biomedical research.
It is important to note that Myriad does not hold patents on the naturally occurring gene in the body, as only a product that is “markedly different” from a product of nature can be patented, as previously ruled in 1911 by patenting adrenaline in its crystallized form isolated from the body, as well as patenting a genetically-modified bacterium in 1980. Rather, Myriad’s BRCA1/2 patents are for (1) the isolated DNA of the genes, (2) fragments for the genes to be used as probes for sequence identity, and (3) a diagnostic test for comparing an individual’s genetic sequence with known mutations/variants associated with breast and ovarian cancer, in which the holder of the gene patent receives a royalty for each administered test. These patents provide Myriad with the right to exclude all others from using their “invention;” only Myriad can conduct the BRCA1/2 diagnostic test and disclose the results of the test to a patient. Because of this monopoly, Myriad charges $3500 for the diagnostic test, which some health insurances will not cover. Furthermore, a patient cannot ask for a second opinion because Myriad claims that their diagnostic test is the “gold standard,” and clinicians and researchers cannot develop new diagnostic tests or even evaluate the accuracy of Myriad’s test.
For these reasons, the ACLU claimed standing to suit based on the technicalities of the test, as well as a violation of human rights. Regarding the diagnostic test itself, Article 35 Section 101 of the Constitution states that a patent can be awarded for a new and useful machine or manufacturing process or an improvement on such a process, or a new composition of matter. Myriad claims that their patent on the isolated DNA is in fact a new composition of matter because the ends of DNA are altered slightly upon extraction. However, the counterargument is that this actually does not matter because the base pair identities are still the same in the isolated form, and this base pair information is what is important for the diagnostic test. Regarding the case against human rights, the ACLU claims that holding a monopoly on this diagnostic test is denying patients of fundamental information and violates the 1st Amendment. Furthermore, the patent restricts progress in conducting research on these genes.
In March 2010, Judge Richard Sweet ruled in favor of the plaintiff because he claimed that there was no actual process involved in the diagnostic test; rather, it was simply a “mental act” of comparing an individual’s BRCA1/2 sequence with other DNA sequences known to be associated with breast and ovarian cancer. Therefore, the patent is not for a new composition of matter and is thus illegal. Myriad appealed this ruling, and in 2011 three judges from the Court of Appeals for the Federal Circuit (CAFC) ruled again: they also said that the diagnostics test was not patentable; however, they ruled against Sweet  2 to 1 on the patentability of a new composition of matter, and thus this aspect of the patent was upheld. The ACLU then appealed to the Supreme Court in early 2012; at the time, the Supreme Court did not look at the case but instead asked the three judges to reconsider their ruling based on another recent case, Mayo v. Prometheus, which disallowed a patent on the process of administering a drug and measuring changes in a metabolite afterwards; this case concluded that anything that retards the progress of science cannot be patented.
Prof. Kevles explained to the Diplomats the importance of understanding the background of the two judges from the CAFC who ruled against Judge Sweet and the one judge who upheld Sweet’s ruling. Prof. Kevles said that the first judge who ruled against Sweet, Judge Alan Lourie, is a former chemist (I’ve never heard of a scientist turned judge, so this was interesting for me to hear!). This judge determined that the “expansive issues” (i.e. the human rights issues) should be excluded from consideration, and that the patentability of DNA should be treated like any other chemical molecule. The second judge, Judge Kimberly Moore, is a former electrical engineer (!) and also said that the isolated DNA was patentable because it has such an obvious use for the biotech industry. Lastly, the third judge, Judge William Bryson, who upheld Sweet’s ruling, used to work in the Department of Justice and stressed the importance of the human rights issues associated with the case, as well as the restriction of the progress of science.
Now that the Supreme Court has agreed to examine this case, how should they rule? The main issue is whether isolated DNA is considered a new composition of matter and can be patented. The patent prevents anyone besides Myriad Genetics from making, using or selling information concerning the isolated DNA of the BRCA1/2 genes and any mutations, variations or rearrangements of this DNA.  There are many stakeholders in this case: on the one hand, competition in the biotech industry can be strengthened with the security that research findings can be patented (and more competition should fuel better research); on the other hand, patients do not have proper ownership over their own medical information, and other medical researchers who may be studying BRCA1/2 may be forced to halt their research due to issues with violating Myriad’s patents.
Prof. Kevles explained that this case boils down to property rights vs. human rights, and that these patents have so far only benefitted the biotech industry and are not for the greater good of cancer research and diagnosis.  He explained that this case has much more at stake than a patent for a new pharmaceutical because you can always develop another drug; however, DNA by nature is “unsubstitutable” and you cannot “invent around it.”  It is also interesting to note that Myriad has had difficulties obtaining patents in Europe, as EU law states that a patent cannot be awarded if it is “contrary to public order and morality.” Prof. Kevles also mentioned that many biotech companies have ownership over other genes, but these companies issue licenses for others to research these genes and have not experienced the same problem that Myriad is now faced with. However, I would be curious to know if these genes are simply “less interesting” or “less controversial” than Myriad’s BRCA1/2. Or, is it truly just as profitable to accrue licensing fees than to have a patent monopoly on a gene?
It is also worth noting that whole genome sequencing technology is actually cheaper (and the price keeps decreasing) than Myriad’s diagnostic test (although sequencing used to cost more before this patent battle started), so any trained scientist could hypothetically  sequence BRCA1/2 (and every other gene) in an individual’s DNA and compare this to the published sequences readily available online. However, the problem is that only Myriad Genetics knows what the appropriate disease variants of these sequences are (without other researchers confirming that the research on these variants is scientifically sound). The nature of scientific research is to have a transparent, peer-reviewed evaluation of your research, and the patents get in the way of this entire process and destroy the foundation of how research is conducted and validated.  Scientific research, especially critical research on cancer diagnostics, is for the betterment of society as a whole, and no company or other entity should have a monopoly on this process. In addition, the civil rights arguments of this case are extremely relevant and should not be ignored; in today’s society, there should be no question regarding whether a patient should have the right to all of his/her medical information using the best diagnostic tools available.
Still, it seems that there needs to be some kind of decision that will not allow for a similar case to be brought to the Supreme Court in the future. As Prof. Kevles said, Myriad does not want these patents just to be “evil;” they have a reason for doing so that they feel is valid. Every biotech company has the right to make a profit from their research, and patents may seem like a secure way to protect their investments for 20 years. However, this case has become so notorious because the genes in question have been linked to breast and ovarian cancer (I’m sure this would not be an issue if Myriad was studying plant genes, for example). I believe that the Supreme Court should decide that different rules need to apply in these situations where human health is at risk, and thus genes that can be used as cancer diagnostic tools should not be patented; this is the only way to allow for progress of scientific research and progress within our society as a whole. However, along with this ruling comes another Pandora’s Box regarding healthcare and insurance coverage for the information associated with an individual’s personal genetic sequence.
This landmark case will be addressed in June 2013, so stay tuned for the Supreme Court’s ruling!

Thalyana Smith-Vikos

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