When the Human Genome Project started in 1990 there were fewer than 100 genes associated with human diseases. The first genetic mutation (for Huntington's disease) was identified in 1986, just a few years before the Project started. After more than a decade of technological innovation and about $3.8 billion, a team of scientists across more than forty research sites succeeded in mapping the entire sequence of human DNA. The project completed two years ahead of schedule in 2003, enabling scientists to sequence the more than 3 billion subunits of the human genetic code. In turn, scientists used the genome to identify sequences and mutations associated with thousands of disorders including muscle disease, deafness, and cancers.
The successful completion of the Project set the foundation for a new era of “personalized medicine” in which genetic information could be used to develop novel approaches in the treatment, detection, and prevention of diseases based on an person’s genetic make-up. There are mutations in the liver, for example, that affect how quickly a person metabolizes drugs, thereby affecting duration and efficacy. For some types of breast cancer there are mutations in a gene called Her2 that respond to the drug Trastuzumab (Herceptin). People without these mutations do not respond to the drug in the same way. Knowing a person’s genetic makeup or the makeup of a tumor, as these cases suggest, has benefits for modifying aspects of treatment for some conditions.
Most treatment options are not so straight-forward. At this point a person’s genetic information has no role in predicting adverse reactions to therapeutic treatments, nor is it possible to customize treatment solely based on a person’s genes. Mapping the genome is a different enterprise than conducting clinical trials for every possible mutation and combination of mutations associated with thousands of different diseases and disorders. Many diseases do not result from a single cause but from a combination of genetic, hormonal, social, and environmental factors.
So while it is possible—maybe even probable—that every person will one day be genomically sequenced, there are limitations to how useful the information will be, and for whom? Consider the so-called "breast cancer genes."
The breast cancer genes, known as BRCA1 and BRCA2 were identified in the mid-1990s. They produce proteins that repair DNA, regulate other genes, and help to keep cells from growing out of control. There are more than 1000 mutations already identified in these tumor supressor genes, and there are likely to be others yet to be discovered. Some of these mutations increase the chances that a woman in the general population will develop breast cancer in her lifetime about five-fold (i.e, from 12 percent to 60 percent). BRCA mutations have also been found to increase the overall risk of ovarian, prostate, pancreatic, testicular, and male breast cancers.
Not everyone who inherits mutations in the BRCA genes develops cancer. But the interactions between genes and other aspects of the molecular environment are not clear enough to explain why. In addition to inherited mutations there are changes in cellular DNA acquired during a person’s lifetime (i.e., somatic mutations) that could tip the scale toward cancer. It’s hard to know how and under what conditions genetic mutations (inherited or somatic) will result in disease. The cancer risks even differ among the mutations of the BRCA genes.
Only 5 to 10 percent of all breast cancer cases and 10 to 15 percent of ovarian cancers among white women in the United States are associated with BRCA gene mutations. This percentage is not especially high, but if a person has a close family member with breast or ovarian cancer and has one of these mutations, other family members may wish to be tested to find out whether it was passed on. Again, a positive test does not mean a person with the mutation will definitely develop cancer. It only identifies an increased risk. The National Cancer Insitute suggests additional monitoring, prophylactic surgeries, chemoprevention, and/or practicing healthy behaviors for people with these mutations. Until researchers know more about how genetic mutations work, however, this fairly limited set of options will remain the norm.
A key goal of the Human Genome Project was to improve tools for data analysis and transfer related technologies to the private sector. "By licensing technologies to private companies and awarding grants for innovative research," says the Human Genome Project website, "the project catalyzed the multibillion-dollar U.S. biotechnology industry and fostered the development of new medical applications. A press release announcing the completion of the Human Genome Project equally stressed the importance of making the data available to the entire scientific community. “Not only does the rapid release of data promote the best interests of science," said Robert Waterston, M.D., Ph.D., of the University of Washington, Seattle, "it also maximizes the benefits that the public receives from such research. From the beginning, one of the operating principles of the Human Genome Project has been that the data and resources it has generated should rapidly be made available to the entire scientific community."
Yet one day after the 10th anniversary of the completion of Human Genome Project (on April 15, 2013), the U.S. Supreme Court heard oral arguments about a case that could prove detrimental to free scientific enterprise. The case of Association for Molecular Pathology v. Myriad Genetics (docket 12-398) entertained whether or not the molecular diagnostic company was legally entitled to patent naturally occurring human genes extracted for the purposes of genetic testing (also known as genetic assay, assessment, and analysis). Myriad Genetics, based in Salt Lake City, Utah, was involved in identifying both of the BRCA genes in the 1990s and were granted patents for those genes in 1998. The company also developed a business model to offer genetic testing for these genes. In the last decade Myriad has grown its diagnostic genetic testing, oncology, and women's health business, with record revenues of $496.0 million in 2012.
But does putting these genes (and the data gleaned from them) in the hands of a single company go against the core goals established by the Human Genome Project? Should human genes be patentable? How would patents impact data sharing, technology transfer, and the availability of genetic data to the entire scientific community? In the case of the breast cancer genes, could patenting "hold a cure hostage?"
In 2009, several women's health groups, researchers, and scientific organizations with a stake in maintaining scientific access to genomic data challenged the legality of seven of Myriad's patents on the BRCA genes. The plaintiffs challenged the patentability of isolated human genes and the comparison of their sequences. The New York judge that heard the case in 2010 ruled that certain of Myriad's patents on the BRCA genes were indeed invalid and improperly granted. The defendants appealed, and a court of appeals partially overturned the original decision in 2011. The plaintiffs then filed a petition in 2012 seeking a rehearing of the case, at which the U.S. Court of Appeals for the Federal Circuit reached the same conclusion as before, ruling in favor of Myriad. The plaintiffs then appealed to the Supreme Court again. This time the Supreme Court agreed to hear oral arguments on April 15th, 2013.
The breast cancer advocacy group Breast Cancer Action was one of the groups contesting Myriad's gene patents and is a plaintiff in the case. On the day of oral arguments, the group organized a rally on the Supreme Court steps to garner suppport and bring attention to the ongoing legal battle. Executive director Karuna Jaggar argued strongly that patenting the breast cancer genes would "block doctors’ and researchers’ access to the human ‘breast cancer genes’ and harm women’s health." Breast cancer survivor and metastatic (stage 4) patient, Lori Marx Rubiner testified that her "life is on the line" while "40 percent of the human genome is already patented, denying information about our bodies and preventing cures." She went on to say that, "As it stands right now, not even my own doctor can examine my genes, and scientists can’t study them, so that Myriad can make money."
These activists have a point. The U.S. Patent and Trademark Office has already approved patents on some 4,000 human genes. The test in question costs anywhere from several hundred to several thousand dollars, and insurance coverage is variable. With exclusive access to the data and the testing process, a company would have the capability to monopolize the market. President and Chief Executive Officer of Myriad Genetics, Inc., Peter D. Meldrum, reported record revenue and operating profits in 2012 and expressed Myriad Genetics' commitment to, "building on this strong performance in fiscal 2013 as we continue to execute on our strategic directives: to grow existing tests and markets, to expand internationally and to launch new tests, including companion diagnostics, across a diverse set of major disease indications."
Clearly, Myriad Genetics has a strong economic and scientific interest in holding the BRCA patents to maintain exclusivity. However, in addition to making the tests inaccessible to many patients and restricting second opinions, growing the market may also mean narrowing scientific exploration.
Nobel Prize winner and co-discoverer of the DNA double helix, James D. Watson PhD, filed an amicus brief arguing that human genes should not be patented on the grounds that human genes are fundamentally unique, that much of what we know about human genes traces back to the Human Genome Project (which was structured as a public works project to benefit everyone), and that patents are not necessary to develop innovative new medicines or biotechnology inventions. "Life's instructions," he writes, "ought not be controlled by legal monopolies created at the whim of Congress or the courts." The sentiment is in line with a 1999 position from the American College of Medical Genetics that gene patents limit accessibility, hinder quality assurance, slow the improvement of tests and techniques, and restrict the professional workforce and training of the next generation of medical and laboratory geneticists, physicians, and scientists.
While the successful mapping of the Human Genome may be cause for celebration, the patenting of genes raises crucial questions about who is to benefit from the explosion of knowledge in genomics and proteinomics. Dr. Robert Klitzman MD, author of Am I My Genes? argues that, "These miraculous discoveries present us too with countless dilemmas, and are far outpacing our abilities to grasp and address their ethical, legal, social and psychological implications." When the Supreme Court rules on the case of Association for Molecular Pathology v. Myriad Genetics in June, it will only consider only one of these countless dilemmas: Are genes a product of nature, or something created out of nature? This answer alone will determine gene patentability in this case, with potentially far reaching implications for patients, doctors, and science itself.
Dr. Gayle Sulik is the author of Pink Ribbon Blues: How Breast Cancer Culture Undermines Women's Health. More information is available on the book's website.
© 2013 Gayle Sulik, PhD ♦ Pink Ribbon Blues on Psychology Today
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