Oncor Med

OncorMed, a medium-size start-up biotechnology company based in Gaithersburg, Maryland, also offered BRCA testing in the research context. The architecture of its testing service, however, differed considerably from GDL's. It incorporated the priorities of a start-up biotechnology company as it paid attention to the concerns of those in the American patient advocacy and biomedical communities who felt that BRCA testing should only be offered through clinical research protocols. Rather than providing testing in order to refine an experimental laboratory technique, OncorMed's protocols were designed to ensure strict attention to counseling and to limit access to high-risk individuals.

OncorMed—a subsidiary of the molecular biology products company Oncor, Inc.—was founded in July 1993 as a company focused on using genetic discoveries and technologies to improve medical care in the area of cancer. Unlike some of the companies that simply looked for disease genes and developed diagnostics and therapeutics based on these discoveries, OncorMed not only searched for genes linked to inherited suscepti bility for cancer and built genetic testing technologies, but also developed medical management tools to help physicians identify individuals who were at an increased risk for cancer and might benefit from the company's technologies. In its 1995 Annual Report, the company stated: "OncorMed provides a valuable linkage between new breakthroughs in cancer genetics and the research and technologies needed to translate these discoveries into diagnostic and therapeutic interventions. . . . We are the gene discoverer's link to one of the world's largest hereditary cancer databases. We are the innovator's link to clinical cancer genetics for promising new technologies, and the physician's link to some of the most sophisticated patient management tools available."35 The company's first product, the Hereditary Cancer Risk Assessment Service (HCRAS), launched in 1994, consisted of a software package and a professional training program designed to help health-care professionals assess hereditary cancer risks.36 Health-care professionals could use the software package to collect family-history information from individuals and display a family pedigree that would determine the pattern of cancer incidence in the family. The company expected that eventually, HCRAS would be integrated with genetic diagnostic services, thereby linking technology and medical practice. This involvement of a start-up biotechnology company in breast cancer genetics research and development, particularly at such early stages of innovation, was a uniquely American phenomenon that had become rather common in the development of genetic medicine, as was discussed in chapter 1. Over a number of decades, the United States had developed a network of laws that encouraged start-up companies to accelerate commercialization of research through both venture capitalist funding and relationships with government-funded academic researchers.37

In keeping with this overall strategy to integrate state-of-the-art technology with medical practice, OncorMed sought to develop a BRCA-testing service and conducted research to find the BRCA genes. The company also decided to apply for patents on its gene discoveries, following the examples of many others in the United States during the 1980s and the 1990s that applied for and sought to use patents on genes to create a proprietary basis for commercialization.38 In one of the most famous cases, the NIH scientist Craig Venter and his colleagues applied for patents on cloned pieces of DNA of unknown function that had been created as part of research linked to the Human Genome Project.39 Although the patent applications stirred considerable controversy and were eventually denied because they did not fulfill the utility criterion set forth by the US Patent and Trademark Office, Venter's attempt popularized the idea that human genetic information could be owned. In fact, after this episode, Venter left the NIH to create Celera Genomics, a company devoted to mapping and sequencing the human genome privately, which joined other companies in selling subscriptions to databases containing human genomic information.

Although it had not been credited with finding either of the BRCA genes, Oncormed applied for patents covering both of them. It had been actively involved in the gene discovery research, using techniques that allowed it to identify a BRCA1 consensus sequence (which was built by sequencing the BRCA1 genes of a number of individuals, and then at the most highly polymorphic—variable—points, averaging the most likely bases to be found at that location to create a full sequence.) This technique generated a different DNA sequence than Myriad's (which was a sequence of an actual BRCA1 gene), and was thus patentable as a separate entity. Multiple patents on the same gene could be granted if they described different gene sequences, which would be entirely possible in the case of the BRCA genes because of their complexity and the multiple mutations possible.40 In this complex patent environment, OncorMed tried to strengthen its proprietary position even further by amassing licenses on other patents covering the BRCA1 gene (and, eventually, the BRCA2 gene). It purchased a license on a BRCA1 patent held by the geneticist Mary-Claire King and her colleagues, which covered a number of markers on the BRCA1 gene, and also negotiated a license on the BRCA2 gene patent held by Mike Stratton and the UK Cancer Research Campaign, the organization who had funded Stratton's research.

In negotiating the license agreement with Stratton, OncorMed agreed to stipulations that would limit its monopoly power and shape the way the patent would be employed in clinical practice.41 The agreement required OncorMed to allow the British NHS to use the BRCA2 gene sequence for testing and future research without paying royalties or license fees, committed OncorMed to sublicense the patent to other companies, and not only specified that individuals be counseled before and after testing but also provided a list of procedures that counselors had to follow.

Stratton's counseling guidelines and desire to couple counseling with laboratory testing fit in well with OncorMed's interest in clinical care.42

This dedication to influencing clinical services, not simply providing stand-alone testing as offered by many companies for other diseases, was also reflected in the company's choice of Patricia Murphy to build and direct its BRCA-testing service. Murphy was a medical geneticist who was board-certified in both clinical cytogenetics and molecular genetics. She had also served as a member of two federal advisory committees, the Task Force on Genetic Testing (TFGT) and the US Department of Health and Human Services' National Action Plan on Breast Cancer (NAPBC) Hereditary Susceptibility Working Group. Both had suggested that much more research needed to be conducted with regard to the clinical, psychological, and social implications of BRCA testing, and that overall, the new technology should only be provided in the context of counseling. Murphy was likely to bring these insights to her work at Oncormed.

Murphy sought to develop a service that would integrate counseling and testing and be acceptable to the medical genetics community. She voluntarily decided to follow the more stringent recommendations offered by the TFGT, by the NAPBC Hereditary Susceptibility Working Group, by ASHG, and by ACOG: OncorMed would offer BRCA testing only in the context of clinical research.

Research was not required by the terms of Stratton's license and the recommendations of these advisory groups did not carry the force of law. In principle, Murphy could have simply offered OncorMed's BRCA-testing service to anyone who wanted it, relying on Stratton's counseling guidelines and OncorMed's previous training efforts to assure that patients received appropriate counseling. The company's role could have been limited to analyzing blood samples and returning results about the client's mutation status to the health-care professional and the client. It also could have developed an approach similar to GDL's, ensuring appropriate attention to clinical care by requiring clients to purchase testing through an academic medical center. OncorMed's restriction of testing to the research context demonstrated concern about the psychosocial dimensions of testing and an interest in building a testing system that was in keeping with the norms and priorities that had been established by the medical genetics community, and it also certified this commitment because the vast majority of clinical research protocols had to be approved by an Institutional Review Board. According to American law, all research protocols conducted by investigators at an institution that receives federal grant monies—e.g., an academic medical center—must be approved by an IRB, an ethics board made up of physicians, scientists, bioethicists, and representatives of the local community.43 An IRB examines all research protocols conducted at an institution in order to ensure that they are ethically sound and scientifically valid. As a private company receiving no federal funds, however, OncorMed was under no legal obligation to require IRB approval of its research protocols, but such approval could implicitly certify the company's commitment to excellent and appropriate health

care.44

Of course, OncorMed was also a private company that needed to turn a profit in order to please its partners and stockholders. How could it reconcile its commitment to limiting testing services to high-risk women within clinical research protocols and its need to generate revenue and produce profits? OncorMed decided to create its own IRB-approved research protocols. According to its 1995 annual report: "Recently, we initiated our own IRB-approved national protocols for hereditary breast, ovarian, and colon cancers and familial melanoma, allowing us to broaden access to these services without compromising our high medical standards or commitment to patient protection."45

Seeking IRB approval for its testing system would allow Oncormed to maintain a balance between its commercial objectives and commitment to excellent care. It could increase its potential market by including individuals who did not have easy access to research protocols at an academic medical center, while also empowering a governing body which could certify that the company operated in the best interests of the users of its testing system. Patricia Murphy described OncorMed's IRB at a Senate hearing on genetic testing by noting that it allowed the company to limit testing to high-risk individuals and ensure that they received appropriate counseling: "OncorMed's protocols are designed to ensure that our susceptibility testing is provided only to people who are at high risk. Patients must be informed about the risks and limitations of the services as well as the benefits. Our protocols require that patients receive genetic counseling both before they are tested and again when the results are known."46 In fact, as the 1990s progressed, more companies involved in research and development in the health-care sector took OncorMed's lead and began to develop IRBs or hire bioethics advisors to demonstrate their commitment to ethical standards in the development of innovation in health care.47

Unlike GDL's system, where IRB approval was only a factor for the fraction of its clients who participated in research protocols, IRBs (albeit multiple ones) would regulate all users of OncorMed's testing system. These regulations covered interactions between principal investigators and clients being tested at academic medical centers, as well as engagements between OncorMed, health-care professionals, and research subjects involved in the company's research protocols.

Overall, Oncormed's system was built by combining multiple, somewhat contradictory, elements of the histories of genetic medicine and health care in the United States. It clearly had commercial objectives, demonstrated by its patenting and licensing of the BRCA genes and development of a commercial testing service. Its architecture, however, also incorporated many of the recommendations that had been articulated by the biomedical and patient advocacy communities as well as advisory committees, such as the provision of testing within research and the integration of testing and counseling.

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