Cracking the 3-billionbase-pair code of the human genome was a critical step toward understanding the genetic underpinnings of health and disease. But it is still several steps away from leveraging this information into a better characterization of, and eventually better treatments for, many common diseases. One approach has been to design large-scale genetic databanks for the molecular study of disease. A number of such projects throughout the world are being planned or implemented.
Pursuing the promise of molecular medicine through DNA banks, however, will rely not only on dedicated researchers, advanced technology, and adequate funding but also on the cooperation of human subjects to provide biological specimens and medical, genealogic, and lifestyle information.
As such research moves forward, investigators must "fully respect human dignity, freedom and human rights, as well as the prohibition of all forms of discrimination based on genetic characteristics," as the UNESCO document, the Universal Declaration on the Human Genome and Human Rights, emphasizes.
Although such international guidelines are important, they are not in themselves sufficient, noted Kirsi Vahakangas, M.D., Ph.D., professor of toxicology and pharmacology at the University of Kuopio, Finland. As Vahakangas pointed out, regulations put in place in 1931 to protect citizens from mistreatment in biomedical research in Germany were not enough to prevent atrocities from occurring under the Nazi regime.
In addition to laws and guidelines, what is also integral to the ethical treatment of subjects in population genetics research is education of the public in the science involved as well as the ethical issuessuch as confidentiality, database access and security, consent, financial and intellectual property concerns, benefit sharing, and oversightthat are raised by this research.
Vahakangas has been involved in promoting the education and discussion of ethical issues in genetic research among investigators as well as the public for many years. She has served on ethics committees and organized symposia on this topic, and she has grappled with such concerns in her own research in the molecular epidemiology of cancer.
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Because science is always moving forward and new situations arise for which there are no rules, Vahakangas said it is up to scientists to keep a dialogue going, to think through the implications of new information and technologies to ensure that the ethics keeps up with the science.
"We cannot rest by getting the laws and regulations passed," said Vahakangas. "We have had disasters in the past because it is difficult to predict what happens next. But we should be prepared to think more deeply and to be empathetic about people to avoid future catastrophes.... Ethical discussion must be ongoing and reach toward the future."
Public Discussion
Including the public in these discussions is key, said David Magnus, Ph.D., co-director of the Stanford Center for Biomedical Ethics and associate professor of pediatrics, medicine, and philosophy at Stanford University in Palo Alto, Calif. He noted that an important element in the success of genetic databanking efforts is making sure that the public understands the goals of the research and how tissue samples will be used. "The public is actually very ignorant about that fact," he said, adding that he is concerned that such misunderstanding could turn into a public backlash against these types of projects.
Such concerns have been taken to heart by the leaders of a number of population genetics research projects. One proposed project, called CARTaGENE, which aims to create a DNA database for mapping the genetic variations of about 60,000 adult volunteers in Quebec, has emphasized the need to treat research subjects as collaborators and participants in the research process rather than as merely the source for biomaterial and medical information.
Led by Claude LaBerge, M.D., Ph.D., director of the Quebec Network of Applied Genetic Medicine (RMGA), a multidisciplinary team from the Genetic Society Project at the University of Montreal has been working since 1999 on the project. In its "Statement of Principles on the Ethical Conduct of Human Genetic Research Involving Populations," the RMGA wrote, "Human rights and ethical principles flow from respect for the inherent dignity of the person. Population research is impossible without the trust of participants. RGMA members consider participants as research partners."
Those involved in the CARTaGENE project are working to engage the community in a research partnership by encouraging an open dialogue among those involved in the project. They have proposed the establishment of a citizen forum to ensure a process of continuous consultation starting before recruitment begins and continuing throughout the research process.
Marshfield Project
In Wisconsin, the Marshfield Personalized Medicine Research Project, a population genetics research project that has been recruiting subjects since the fall of 2002, has also recognized the importance of engaging the community in its research.
"From the beginning, the project leaders knew they needed strong public understanding and cooperation to get participation," said Norman Fost, M.D., director of the program in medical ethics at the University of Wisconsin Medical School in Madison and chair of the ethics and security advisory board of the Marshfield project.
The project leaders worked with focus groups to raise public awareness and address public concerns about the project. "They wanted to do everything they could to make sure the population that would be involved in the study knew about it and were familiar with it and had a chance to have their questions about it answered," said Fost.
The Marshfield Clinic serves virtually the entire population in Marshfield, a town in central Wisconsin, and the surrounding area, called the Marshfield Epidemiologic Study Area, said Cathy McCarty, Ph.D., director of the Marshfield Clinic Personalized Medicine Research Center and coprincipal investigator for the project. Subjects 18 years and older are being recruited to donate DNA, serum, and plasma samples, which will be matched up with their medical information to create a powerful, secure database for genetics research. So far, about 17,500 people have been recruited, said McCarty.
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Before they began the project, the investigators consulted with a community advisory group to gather their input on the project. In the first meeting, McCarty said that many of the community members expressed doubt as to what they could add to the discussion. "But by the third meeting they were so excited," she said. "They got it and saw how they could contribute by providing their perspective on the project in ways such as sharing feedback with the researchers on how to best convey information about the project's mission through posters and fliers."
Fost noted that many of the ethics-related concerns the public initially raised were based on misinformationsuch as the project would involve cloning, which it does notand therefore public education efforts have been key in the success of the project. "My favorite motto is that good ethics begin with good facts," he added.
Cancer Specimens
Echoing the emphasis on education and community engagement, Julie Schneider, D.Phil., technology program manager in the Office of Technology and Industrial Relations at the National Cancer Institute, said that communication and outreach to the public is an integral piece of putting together a national repository for tumor biospecimens linked to clinical dataa recently proposed project called the National Biospecimen Network (NBN).
Schneider noted that cancer researchers face a number of challenges in terms of access to the large numbers of high-quality specimens and clinical data needed to take advantage of new genomic and informatics. Tissue repositories across the country do not follow standardized procedures, nor are they connected by a common informatics platform, a situation that impedes large-scale interinstitutional genomic and proteomic investigations, said Schneider.
The NBN is an effort to overcome these obstacles. A blueprint for the network was drawn up recently by a diverse group of individuals from the cancer community, including the NCI, as a way to standardize collection, processing, storage, and annotation of biospecimens and allow for their distribution while ensuring the privacy of donors.
"The management of ethical and legal issues obviously will be critical for the system," said Schneider. For example, consent is a key issue in the process. But consent is more than just filling out a form; rather, it is a process, a dialogue, about how biospecimens will be used, she said.
To that end, the NBN project designers have emphasized efforts to educate patientsas well as the public and stakeholdersabout the research and to address ethical issues, to generally help people understand the whole process, said Schneider.
The designers of the network envision a "chain of trust" to support the relationship that exists between patients and researchers and includes everyone involved in the system, from surgeons and pathologists to members of internal review boards.
"The chain of trust model starts with a very badly needed education process," said Anna Barker, Ph.D., deputy director for advanced technologies and strategic partnerships at the NCI. "I think we in science need to do a much better job of having patients understand the value of these resources to genomics- and proteomics-based research. In fact, that is the material of the biomedicine we are proposing for the 21st centurythat personalized medicine actually is going to be totally dependent on these types of resources," said Barker.
Whereas the national network is only in the planning stages, pilot projects are already under way that will serve as crucibles to work out various issues such as standard operating procedures, quality control measures, informatics, access to resources, and ethical and legal challenges before a larger national database can be developed. As Barker said, "I think it's an initiative whose time has come. We just have to carefully plan for it and ensure that we're taking into consideration everyone else's ideas and thoughts on it."
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