Biobanks for Breakfast

On April 25, 2008, a collection of community leaders, top medical researchers, and statewide biotech industry leaders met to discuss the bioethical and legal issues surrounding biobanks in Indiana. Biobanks are a growing resource in biotech research. They contain samples of human biological specimens and are often linked in varying degrees to the personal health and demographic information of the donor. Biobanks range from the very small disease specific collections of tissue to the very large national sponsored banks of several million specimens incorporating several different types of biological material from persons both healthy and with known disease. Ownership and commercial involvement are among the most difficult ethical issues in developing successful biobanks. The Bioethics for Breakfast group considered these issues along with Indiana’s role in future biobanking by asking attendees to think about the following questions:

- Are you willing to donate your DNA to a biobank for medical research?
- Are you comfortable allowing Indiana companies to profit by developing commercial products from your samples and donations?

Guest speakers at the event included:

David Flockhart, M.D., Ph.D. , Chief of the Division of Clinical Pharmacology at the Indiana University School of Medicine – Dr. Flockhart outlined the national and international status of biobanks.

Mervin C. Yoder, Jr., M.D., Richard and Pauline Klingler Professor: Department of Pediatrics, Indiana University School of Medicine – Dr. Yoder discussed the therapeutic use of biobank samples.

Andrew R. Klein, J.D., Paul E. Beam Professor of Law, Indiana University School of Law - Indianapolis – Prof. Klein led the group in discussion of the difficult ethical and legal issues.

The Bioethics for Breakfast series is co-sponsored by the Indiana University Center for Bioethics and the law firm of Sommer Barnard. – Patrick Barrett

Genetic Research - Up to the Task? Educating Health Care Providers

In lively exchanges between bloggers from Gene Sherpas, Genetic Future, and Venture Beat, the ethical implications of private genetic testing and personalized medicine were explored and a number of issues were spotted (see comments from Steve Murphy, David P. Hamilton, and Daniel MacArthur). I find Steve Murphy’s compelling suggestion that physicians in clinical practice lack the time and interest to provide thoughtful guidance to patients on genetic testing and test interpretation both relevant to PredictER's program and worth further assessment.

Like nearly every other academic medical center in the United States, Indiana University (PredictER's home) is interested in determining what a large scale predictive health study would look like. More clearly, researchers are asking: what needs to be in place for a large study to successfully combine genetic information along with other health data and biographical information? To be sure, it could serve as a platform for researchers in almost any biomedical research field, but more to Steve’s point, is it practical or possible to role out a study of this kind in clinics and doctors offices? Is there enough interest and enough time for a primary care doctor to attend to this new type of information?

If there's a deficit of interest and time, this is the moment in which the life sciences community should work to develop both. This not so much a disagreement with Steve’s suggestion as a statement about the ultimate goals of predictive health--there is no doubt that the clinical world of primary care is already pressured to the point of precluding physicians from developing new interests or allotting additional time in their schedules, but balance this fact with the knowledge that the outcomes of predictive health remain to be measured. As the prevalence and usage of these tests increases, so will the understanding of how they are being used and interpreted. So, while many are interested in fostering new research platforms to identify targets for new tests, others (including PredictER) are interested in laying a foundation of ethics outreach, education, and assessment to guide the realization of translational science and personalized medicine. One strategy might be to engage busy, primary care doctors with incentives to pursue relevant continuing medical education prior to initiating fully integrated predictive health projects. To do so, one would need a flexible, responsive curriculum (perhaps an online learning module) available for any physician whose patients are or might be enrolled in a predictive health research study ... but what would issues and subjects would such a curriculum need to address? Here are a few that leap to mind:

- Structure of Predictive Health Studies
A bank containing genetic samples and future research projects drawing on this
- Longitudinal research: from Framingham to today
- Impact on Practice in Primary Care
Personalized medicine: prevention, prognosis, pharmacogenetics
- Ethical Issues
Informed Consent
Vulnerable populations
Confidentiality
Recontacting patients
Withdrawal
Return of genetic information
Selling genetic information

I'd be interested to see how PredictER Blog's readers would change this list. What do primary care physicians need to know? Any ideas?

Predicting a New Disease: Pathological Consumption of Genetic Information

The current issue of the New England Journal of Medicine (10 January 2008; PMID: 18184955) contains a cleverly titled article “Letting the Genome out of the Bottle – Will We Get Our Wish?" The article, which explores the new phenomena of commercialized personal genome analysis through genetic profile tests capable of identifying several hundred thousand variations in any one genome, has drawn the attention of several astute bloggers, including: Myles Axton of Free Association, Blaine Bettinger of The Genetic Genealogist, Hsien-Hsien Lei of Eye on DNA, and Steve Murphy of Gene Sherpas. The general conclusion of the NEJM authors is that perhaps a person may get their wish, but the clinician certainly won’t. Why is that? Because the predictive value of many of the variations identified by the tests is questioned as is the utility of the information itself, i.e. what will the patient do with the information? While both of these arguments are accurate, they need to be tempered with common sense and a degree of humility rarely found when scientists address general society.

Beginning with the first point, the predictive value of these tests is limited. Lead author Dr. David Hunter develops this point in a US News and World Report interview with Nancy Shute (Why Not to Buy a Scan of Your Genome, 9 January 2008). Hunter notes that the predictive value of many of the genes or single nucleotide polymorphisms (SNP’s) found in these genetic profiles pales in comparison to the predictive value of tried and true genetic tests for specific genes like BRCA 1 and 2. To be sure, he is correct, but interestingly the predictive value of the BRCA gene is being called into question this month as well. A large population-based case-control study published in the Journal of the American Medical Association (Begg CB, et al. Variation of Breast Cancer Risk Among BRCA1/2 Carriers. JAMA. 2008;299(2):194-201. PMID: 18182601) suggests the BRCA 1 and/or 2 gene alone may not be as predictive as once thought, and that a variety of other genes may explain the strong familial clustering of breast cancer. What this means is that the more we know about genetics, the more we recognize the limits of our knowledge. How then can adding personal genome profiles adversely affect this pool of knowledge?

Moving now to the second point: the clinical utility of general genome profiles is questionable. Certainly this is the case. Still, the authors need to keep "personal" aspects of these profiles in mind. This is not a test marketed to health professionals to guide treatment; it is a test marketed to guide lifestyle, a type of guidance which most physicians are admittedly poor at providing for their patients anyway. Further still, the lifestyle changes dictated by carriers of the BRCA gene may be very dramatic—possible removal of both breasts and ovaries; contrast these to the lifestyle changes encouraged by a personal genome scan indicating an increased risk for heart disease—increased exercise and proper diet.

In sum, Dr. Hunter and his colleagues are right to raise their concerns about these tests: the tests have limited capability, unknown utility, and are expensive. Still, the capability of any medical test can only be magnified by an increase in data. Furthermore, an unknown clinical utility does not mean that a person cannot derive some utility from knowing their own genome profiles. If this were the case, why would they purchase the test at all? Perhaps Dr. Hunter’s lament is in part that the human genome, once the bastion of modern orthodox medical science, now will be shared with alternative medicine in a very real and technical way. Making this point clear is what is necessary, not admonishing patients on how to spend their money. - Patrick Barrett

Engaging the Community in Predictive Health Research: Reporting on PredictER's November 2nd Expert Panel

Research and the Community

In most predictive health projects, researchers need to obtain human biological materials that can be stored for immediate or later use and then linked to detailed health information from medical records. Building biobanks and predictive health research projects requires a supportive public. To succeed researchers need a representative sample of willing participants, good state and institutional policy, and (of course) funding. (This research also benefits from highly motivated advocacy groups such as Susan G. Komen for the Cure.) In a few words, predictive health is one of the most community saturated forms of medical research to date.

Ethical Issues

The great good that will be accomplished by predictive health research, with its ability to forecast a person’s health future with reasonable probability, must be pursued with careful consideration. These studies raise ethical, legal, and social questions beyond the scope of the current paradigm of medical research. Very basic examples of these questions include: What do researchers do when they find that an individual tests positive for a gene or other biomarker that puts them at significant risk for a disease in the future? Can an individual’s biological material be used first to study one type of disease or treatment and then later another? What protections need to be in place to ensure that the sensitive information in an individual’s health record and genes does not result in employment or health insurance discrimination?

The Pace of Translation

While questions like these may seem very scary when rattled off one after the other, the truth is that predictive health is the future of medicine--a future that hopes to fulfill the ambitions of the human genome project, by providing an individual with a personalized assessment of risk and response to treatment. The human genome project succeeded in decoding a great deal of information, but what that information means for individuals with heart disease, a family history of cancer, or a smoking addiction, has not been answered. If current research succeeds, this information will be translated into real clinical applications in the not too distant future. Research looking to define these types of predictors is well underway at most universities--some, as exemplified by Emory's Predictive Health Initiative and the TGen (Translational Genomics) project in Arizona, have worked to establish comprehensive predictive health research programs. Meanwhile, as The Wall Street Journal recently reported many (up to 1,400) genetic tests are already available for individuals interested in assessing their risks for a number of diseases. Moreover, many specific predictive tests are already being used to chart treatment paradigms in hospital care.

PredictER Engaging the Community

Still, the fact that predictive health is occurring does not answer any of the concerns voiced earlier. These are concerns that the PredictER program at the IU Center for Bioethics is working to address. On November 2nd, PredictER convened a panel of 35 experts and community advocates to begin to give shape to many of these concerns and to explore ways to reach out to the community, build collaboration, and encourage research while protecting individual and public interests. While the panel of experts shared an understanding of the progress of predictive health, it took an entire day of brainstorming and discussion to reach consensus on what issues may be present with respect to engaging the community. In the end, it was clear that predictive health will require physicians, researchers, and the community to join in constructive, mutually beneficial work. In the near future a white paper will be published by the Center for Bioethics with a more detailed account of the November 2nd event. This paper will also introduce the next step in PredictER's community outreach mission--a plan to engage central Indiana community leaders and to listen to their concerns about the future of predictive health research. -- Patrick Barrett

Predicitive Health & Medical Education: Lost in Translation

When reflecting upon the greatest medical advancements in the last fifty years of medicine, certain broad and worthy categories come to mind. Imaging technology, drug design, and minimally invasive surgery have made great changes in how patients are treated. As a fourth year medical student, I routinely request a CT, suggest a regimen of Gleevac, or recommend a laproscopic procedure. All of these advances have made waves in the practice of medicine, public expectations, and medical education. Predictive health research, however, has not yet fully entered the medical school curriculum.

I doubt whether there is a single undergraduate who gains acceptance to medical school who cannot identify the names Watson or Crick or explain the basic function of DNA. By now, most students are also aware of the recent completion and publication of J. Craig Venter’s genome. Nevertheless, discussions with my peers suggest that medical students may not be fully prepared for the medical and ethical implications of recent genetic research. Predictive health research discoveries are taught, but the potential clinical applications are lost in translation--stuck somewhere on the path from the bench to the bedside . . . or, in my case, from the pages of the textbook to the patient.

For my generation of medical students, predictive health research has the potential to significantly change the practice of medicine. While programs like the Personal Genetics Education Project at Harvard are building interest in predictive health, and while the public is flooded by a confusing array of genetics news reports, what are medical schools doing to prepare future physicians for the predictive health revolution?

Medical students and educators should step up their efforts to join the conversation about the clinical promise and ethical issues of predictive health. We need to start thinking and talking about how we make use of the predictive tools we already have and how we will prepare for future tools. For example, how many of us are ready to explain to new parents the meaning of normal newborn screening results? Are we fully prepared to share the non-watered-down reasons for why we may want a fifty-year old man to get a colonoscopy? Are we ready to address the anxieties of a patient considering a genetic test to better determine her risk of breast cancer? Clearly, students and bloggers like Bertalan Meskó at ScienceRoll are doing their share to spread the word, but we should encourage our mentors and professors to join the discussion. What is the current state of predictive health, and where can we expect it to advance?

[Note: To encourage a public discussion of the ethical, legal and social implications of predictive health research, PredictER Blog will be inviting guest contributions from students, professionals, and interested members of the public. This post from Pat Barrett, a fourth year medical student at the Indiana University School of Medicine and a graduate student of the Indiana University School of Philosophy, is a fitting introduction to this new feature of PredictER Blog. -- J.O.]