Summary of August 1, 2001 Meeting

Ethics and Intellectual Property Meeting Summary

The morning session of the meeting began with professor Jon Merz providing an overview of the purpose and use of gene patents and key cases illustrating their impact on research. He was followed by Eric Johnson, Ph.D. who discussed the need for identifying common ground between academic researchers and research sponsors. The afternoon session included formal and informal case discussions and a closing talk by Arthur Caplan, Ph.D. on the politics of stem cell research. 

Morning Session

After participant introductions, the meeting objectives were reiterated:

• to educate participants about pertinant intellectual property issues
• to share experiences and agendas of disease-specific organizations
• to discuss the necessity of subsequent phases of the Center for Bioethics project
• to develop a disease advocacy group network for intellectual property issues
• to begin the process of bringing intellectual property issues before the legislature

Professor Merz started the meeting by making an initial distinction between genes patented for diagnostics, where one form of a gene is clearly associated with one disease, and gene sequences patented for therapy, where the association between the genes and their use is much less clear. Because a patent confers exclusive ownership to a discovery, both have the potential to restrict research and clinical use of the genetic discovery. The latter, however, is particularly problematic because it prematurely hinders the progress of collaborative research. 

Discussion was spurred by Professor Merz's brief presentation of a number of cases that provide practical examples of how disease-specific organizations have confronted intellectual property issues. 

Canavan Disease Canavan Disease is a rare, recessive disease that strikes the brain of affected children, typically resulting in death by the early teens. Many Canavan-afflicted families actively participated, secured the participation of other families, helped raise funds, and worked in a close collaborative relationship with a researcher to discover the gene. The researcher's institution, Miami Children's Hospital (MCH) patented the diagnostic and other uses of the gene, and then instituted a licensing program that greatly restricted access to the gene. The families were indignant at the fact the patent was sought without their knowledge, and upset with the way it was used. After trying to negotiate with MCH, they decided to sue the hospital in October 2000 in an attempt to prevent continued misuse of the patent. The case is, as yet, unresolved.

Hemochromatosis Hemochromatosis is a recessive iron overload disease that causes slow iron buildup in the cells of bodily organs, leading to diabetes, heart, liver and other organ failure in middle age. The gene HFE was discovered by a company in 1996, and patents were issued in 1998. The patents were licensed exclusively to SmithKline Beecham for clinical testing services, but subsequently have become the property of Bio-Rad, Inc. Bio-Rad is selling a test kit for the most common gene variants that cause disease. It is unclear how this kit will affect the ability and costs for laboratories performing HFE tests.

Breast Cancer The two known genes that cause breast and ovarian cancer (BRCA1 and BRCA2) were patented by Myriad Genetics in the US and elsewhere in the world. Myriad has monopolized genetic testing for these two genes in the United States, and may attempt to do the same in Europe.

Alzheimer's Disease A variant of the Apo-E gene was discovered to be related to late-onset Alzheimer's disease, and the genetic test for the purpose of diagnosing a patient's Alzheimer's status or risk was patented by researchers at Duke University. An exclusive license was granted by the University to Athena Diagnostics. Athena has secured exclusive licenses to numerous genetic tests for neurological disorders (including Charcot-Marie-Tooth disease and Spinocerebellar Ataxia), and has aggressively prevented other laboratories across the US from performing testing for these genes.

Pseudoxanthoma Elasticum PXE International, created in the mid-1990s, created a DNA bank and raised money to support studies using it. The foundation negotiated with researchers to whom they provided support and access to biomaterials for research. Through use of Material Transfer Agreements, PXE International retained authorship of any papers and ownership rights in any patents in order to ensure broad and affordable availability of the test and to retain influence over downstream development. The gene implicated in the disorder was identified in early 2000.

Alpha-1 Antitrypsin Deficiency The Alpha-One Foundation was created to expedite research into therapies and a cure for Alpha-1. The foundation has provided monetary research support, created a confidential research registry as well as a DNA bank, sponsors annual research symposia, and helped secure funding for a program and faculty chair at the University of Florida. The Foundation is developing proactive policies that will best protect the interests of the Alpha-1 community in new discoveries resulting from collaborative and sponsored research, while directly promoting research for treatments and a cure.

Group Discussion 

Participants actively engaged in discussion after the case presentation. 

• " A genetic researcher said, from his experience, patent applications do not apply to research projects. Researchers tend to ignore ownership rights to genes, but this is only possible when the research does not have significant commercial potential.
• " An officer of an advocacy group said that if a genetic discovery cannot help his daughter because it is tied up in court for ten years, it is as if it was never discovered because the benefits are inaccessible.
• " The president of an advocacy group, a mergers and acquisitions lawyer by training, explained that the American Bar Association is spending time and money on the issue of biotechnology patents. Interfacing with them might be a good idea. He explained that for small biotech companies, patents are a big deal because they are their principle assets. Because these companies are required to disclose assets, the public has access to useful information.
• " A participant expressed concern over the fee Myriad Genetics is charging for clinical BRCA1 testing. Professor Merz explained the patent is not limited to clinical use of BRCA1/2 - it affects breast cancer research as well. Because of the patents, Myriad has been able to define the types of testing that are considered research. Myriad prevented National Cancer Institute (NCI) funded laboratories from performing BRCA sequencing under research protocols in late 1998. In response, NCI and Myriad entered into an agreement under which Myriad will perform genetic testing for NCI funded researchers at a reduced cost. 
• " The president of an advocacy group said he would like more research to be conducted on his disease and he is aware that researchers want access to large amounts of tissue. He is concerned, however, about the rights of his disease community regarding tissue donation and anonymity/privacy. What do patients need to know? He would like a forum such as the one convened by the Center for Bioethics to address these concerns.
• " Numerous participants expressed the need for the development of white papers that discuss, on an elementary level, the issues to which patient advocacy groups should be aware. 
• " It was asked whether any non-profit organizations have taken a position on the issue of gene patenting. This question is discussed below.

The Common Ground: Academic, Biotech and Consumer Partnering for Enhanced Research Outcomes
A presentation by Eric Johnson, Ph.D., a researcher at Barrow Neurological Institute who spoke on behalf of Genetic Alliance.

Dr. Johnson explained that Genetic Alliance is the largest international coalition of families, researchers and health professionals dedicated to meaningful progress in genetic research, policy and services which requires active and informed consumer involvement. Genetic Alliance believes consumers ought to on the ethical conduct of research development of intellecual property. He went on to say that few people will get rich treating the vast majority of genetic disorders because they are rare, but the alliance seeks to represent their needs as well as those genetic disorders where treatments wield great commerical potential. Genetic Alliance sees patients, families and support groups as full and equal partners who are all interested in moving research-related intellectual property into the marketplace. The Alliance is not opposed to gene patenting, the practice is regarded as pragmatic.

Dr. Johnson believes that most clinicians are "blissfully unaware" of the genetic advancement and its potential impact on individuals and families. The relationship between patients and clinicians has thus changed because patients have become savvy health care consumers who often know more about their disease than their clinicians. While clinical education is needed, patients are helping in this regard.

Johnson explained the evolution of his own perspective toward gene patenting. Initially, he was opposed to the practice because it seems counter to the scientific mission. When he discovered a gene believed he made a morally correct decision to publish the discovery without filing for a patent. Now, a group of European scientists are working to patent this gene that he and his colleagues discovered. Today, he sees patenting his discoveries as a necessity in order to protect their future use. It costs approximately $20,000 to patent a discovery, however, which is a lot to researchers not associated with "big pharma". He does not believe in slamming the doors on the biotech industry, however, He sees large companies as viable avenues for researchers and groups to travel in order to move medical discovery ahead.

Johnson provided advice to disease-specific groups. It is important not to "PO the PI", meaning when there are only a few researchers, perhaps in the world, that are researching a particular disease, it is important that disease avocacy groups do not behave in ways that will alienate the only people who are willing to move their research ahead. One thing to watch out for is taking exclusive ownership of their discoveries.

Johnson presented the PXE model of blood and tissue bankis. PXE is establishing a "consumer centered, managed, and focused" DNA bank through Genetic Alliance that will be used for research on rare diseases. A central IRB is being established to handle tissue collection and anonymity issues and a lay community of patients will be established to assist the IRB. The PXE DNA bank was initially housed in Harvard University, but when Harvard would not share access to the bank, it was moved to the lab of Eric Johnson who managed the samples gratuituously. 

He went on to say that while researchers do become emotionally invested in the community for which they are researching, they often prefer to stay a little detached.

When patient advocacy groups hold the code to DNA samples and have their own IRB to oversee research, researcher receipt of anonymized samples relieves the researcher of the IRB burden at his/her institution.

When scientists disseminate findings, the involovement of patents make the determination of intellecutal authorship much more selective. At this point, another participant said that her advocacy group demanded authorship on a paper because if it was not for the insistence of her community that the disease was genetic, the paper would never have been written. She also said that the researchers needed her group in order recruit subjects for study. 

Johnson was asked about the average yield of DNA - what does he do when he runs out of DNA? Does he draw more blood? Reconsent? He said that while this has not been an issue yet, it raises concerns about the difficulty of obtaining consent from international donors.

Afternoon Session

Protecting the Interest of Patients and the Public in the Commercial Biotechnology Marketplace: the Case of Alpha One - a presentation given by Miriam O'Day, a representative of the Alpha One Foundation.

Alpha-1 is a genetic, pediatric liver disease caused by a single gene that, in the absence of a liver transplant, causes chronic emphysema. The treatment for the lung disease is plasma replacement therapy, which is in short supply. The Alpha One foundation is research focused; its mission is to provide leadership and resources to alpha-1 research. The foundation operates a tissue bank, research registry and screening test and is very mindful of bioethics issues, including confidentiality, consent, use of data, treatment of human subjects and familial linkage studies. While they understand that neo-natal screen raises serious ethical concerns, these are outweighed by the costs of delaying the start of preventive measures.

The Alpha One foundation owns their research registry which is housed by Medical University of South Carolina. Researchers requesting access to the registry much submit IRB approved protocols to the foundation for review. Patients with information in the registry are contacted five to six times per year by registry staff to obtain consent for the use of their information in studies. 

firewall can protect confidentiality of donors but is expensive

Group Discussion

• " The president and chief researcher of a disease-specific organization was concerned that research at her institution was very informal with no mention of firewalls and other intellectual property issues. She fills many roles for her organization. She collects DNA and manages the registry, works with the parent support group, and conducts research. She said if she did not do this, research on her disease would not be conducted. Now, things are becoming complicated, with labs always requiring consent forms samples when many of her donors are from overseas. 
• " A participant responded that HIPPA would surely impact her research program but the research community was frighteningly silent when the legislation went through. Now a law is in place that is poorly understood and adhered to by researchers.
• " Another participant responded, saying that she has the option of removing all identifiers of the samples, but then the use of the samples is then limited. 

Distinctions were then made between anonymized, coded, and unidentifiable samples.

Anonymized samples are tissues that are stripped of the donor's name...

Coded samples are tissues for which the name of the donor has been replaced with a code, and that code can then be traced back to identifying information about the donor.

Unidentifiable samples are not linked 

• " A participant asked how consent is obtained when a tissue donor is deceased. Does the executor of the estate give consent? Dr. Merz replied that, according federal regulations, an identifiable tissue is considered a human subject. dead people are not human subjects, expectation of privacy, identifiable, living, relatives might be human subjects
• " A participant explained that the research registry created by his organization lead to the discovery of the disease gene which is now owned by Johns Hopkins University. While he believes it has not exploited (yet), it costs $900 per test and is only available through clinical trials. The thing he finds most problematic is the absence of a pre-natal test because there is a direct correlation between presence of this gene and onset of the disease. 
• " David Magnus, Ph.D. pointed out that aftern a patent is issued, patients have little control and, very often, decisions are made according to business rather than public health.
• " A participant responded that this practice is imply unjust enrichment, that it is unethical to the group providing access to the research.

Stem Cell Research: Current Debate, Future Policies
A closing talk given by Arthur L. Caplan, Director, Center for Bioethics.

Since much as changed in stem cell policy since the August 1st meeting, we have included a more timely article for your review.