California Department of Public Health Orders Changes to Berkeley's Genetic Test Program

Last week Berkeley altered its Bring Your Genes to Cal Program to stop the genetic test results from being disseminated back to participating students in response to an order from the California Department of Public Health (CDPH). Berkeley will still hold discussions and lectures based on the aggregate information as previously planned. [See our posting on the Bring Your Genes to Cal Program here.]

On August 11, Berkeley and CDPH met to discuss the program’s compliance with the California Business and Professions Code which requires that a physician order clinical laboratory tests. In a statement to CDPH, Berkeley asserted its program should fall under an exemption for labs performing tests as research where the results are not reported to patients as part of a medical or health assessment. Berkeley maintained that these statutory requirements were not applicable to its program because Bring Your Genes to Cal constituted an “educational experiment,” students are not “patients,” and the three specific gene variants tested are not disease related.


Despite these claims, the program would have returned genetic test results back to each student, which should be defined as part of a health assessment because the program directed students to use these results to inform their dietary and nutritional choices as well as make personal health decisions. According to Dean Schissel’s message to students in the informed consent video, these genetic test results would then allow them to take measures to improve their health such as eating more or less of a particular food, or avoiding alcohol if their test results showed an ethanol “allergy.” Schlissel’s assertion stretched the meaning of California’s exemption in denying that this “experiment” constitutes clinical laboratory tests or that this information is medically significant. Arguments over statuory construction closely parallel the current federal regulatory loopholes relating to DTC genetic tests.

As genomeweb observed, the semantic debate between Berkeley and CDPH is strikingly similar to the volleys between CDPH and DTC genetic test companies that occurred back in 2008. In June of 2008, CDPH had responded to consumer complaints and sent out thirteen cease and desist letters to DTC genetic testing companies, asserting that their policies did not comply with licensure requirements set forth in California law. Two of the targeted companies, 23andMe and Navigenics, asserted they offer an “informational service” providing personal genetic information and not “medical testing services,” so they did not need to obtain a license. CDPH agreed and granted licenses to Navigenics and 23andMe in August 2008.

Now, with Congress and the FDA scrutinizing the federal regulatory requirements, CDPH seems to be responding to the current political shift of opinion and the uncertainties related to providing genetic test results without a physician intermediary and oversight of the test's accuracy and validity. Or perhaps CDPH agreed with concerns in the defeated California Assembly Bill 70. This bill would have urged state schools within the California State University and University of California system from requesting students’ DNA for the purpose of genetic testing.

Defeated AB 70 also raised specific privacy concerns stemming from a university collecting students’ DNA samples for genetic testing and retaining students’ coded genetic information. Although Berkeley's program will incinerate students’ DNA samples following testing, it plans to keep students’ genetic information for further study. Data attack in GWAS studies exemplifies the principle that our understanding of data security relating to genetic information is uncertain, and we have continually underestimated the potential for security breaches. Dean Schlissel’s unwavering promises of absolute privacy seems naively optimistic given what we know in this area.

It seems this “teaching study” has given Berkeley and its freshmen more than they could have anticipated. In addition to the campus lectures about genetics and personalized medicine, students have already learned the ethical and legal complexities associated with emerging technology- the varied parties who have a say, the definition debates, and the unpredictability of the resolution.

--Katherine Drabiak-Syed

Data Sharing and Privacy: In the News

Roughly one year after the NIH and The Wellcome Trust restricted access to genome-wide association studies [see: Modifications to Genome-Wide Association Studies (GWAS) Data Access (NIH, August 28, 2008 - PDF)], data sharing is back in the news. In August, researchers in Tel Aviv and Berkeley announced a new method of protecting the privacy of individuals in genetic research studies. In the press release, one of the authors, Eran Halperin, alludes to the PLoS Genetics paper that led to the NIH's data access modifications (Homer N, et al.). As Halperin sees it, the "knee-jerk response stymied potential breakthrough genetic research." Perhaps he hopes that the new privacy approach will re-open the doors of safe data sharing. Halperin's method (published in Nature Genetics) uses a likelihood ratio (LR) test to measure the risk of exposing a single individual within a data set. Ultimately, the LR test limits the number of SNPs shared and thereby decreases the chances of privacy losses. If you would like to give this method a try, the software is available online (with registration) at SECUREGENOME.

In related news, The Toronto International Data Release Workshop (Genome Canada, May 2009) recently recommended the "rapid release of prepublication data" to speed the pace of scientific discover. The recommendation was published in a special, data sharing edition of Nature. The Workshop cites the Human Genome Project as an example of how sharing data leads to public benefits: "This experience ultimately demonstrated that the broad and early availability of sequence data greatly benefited life sciences research by leading to many new insights and discoveries, including new information on 30 disease genes published prior to the draft sequence." In a note addressing the human subjects concerns, the Workshop acknowledges the privacy risks: "Data about human subjects participating in genetic and epidemiological research require particularly careful consideration owing to privacy-protection issues and the potential harms that could arise from misuse. ... [F]or clinical and genomic data that are associated with a unique, but not directly identifiable individual, access may be restricted."

Will these developments (a proposed technical solution to the privacy barrier and a reaffirmation of the social benefits of data sharing) encourage the NIH and The Wellcome Trust to reduce some of the restrictions on data sharing? (I’d say: not yet.) While the safety of data sharing may be increased with technical solutions, it seems unlikely that all privacy risks will be eliminated. After all, if I share something "private" with you (or with anyone else), it's not so "private" any more. At the same time, if data access is restricted (for example, by using smaller, "safer" data sets), the public benefit of sharing resources declines. Clearly, we are looking for a way to eat our cake and have it too; protecting the individual's privacy while sharing for common benefits. Perhaps we should ask ourselves, what are the risks that we are willing to impose on individuals for the benefit of the common good? As an individual, exactly how private is your privacy? And at what cost?

References:

Homer N, et al. Resolving individuals contributing trace amounts of DNA to highly complex mixtures using high-density SNP genotyping microarrays. PLoS Genet. 2008 Aug 29;4(8):e1000167. PMID: 18769715

Sankararaman S, Obozinski G, Jordan MI, Halperin E. Genomic privacy and limits of individual detection in a pool. Nat Genet. 2009 Sep;41(9):965-7. Epub 2009 Aug 23. PMID: 19701190.

Toronto International Data Release Workshop Authors, et al. Prepublication data sharing. Nature. 2009 Sep 10;461(7261):168-70. PMID: 19741685.

Other Predictive Health Ethics News

Nikki Tait. Pan-European biobanking moves closer. Financial Times. September 16, 2009.

Michael Rugnetta and Whitney Kramer. Paving the Way for Personalized Medicine. Science Progress. September 14, 2009.

Daniel Vorhaus and Lawrence Moore. What happens when a personal genomics company goes bankrupt? Genetic Future. September 14, 2009.

Caroline Wright. HGC public consultation on DTC genetic testing services. PHG Foundation News. September 8, 2009.

Over Ninety Per Cent Of Pathologists Find Research Rules Too Complex. Medical News Today, September 8, 2009.

Jane E. Brody. Buyer beware of home DNA tests. The New York Times. August 31, 2009.

Brad Therrell, Harry Hannon, Don Bailey, et al. Considerations and Recommendations for a National Policy Regarding the Retention and Use of Dried Blood Spot Specimens after Newborn Screening. Genetic Alliance. August 21, 2009.

Turner Ray. Lack of Physician Education, Genetic Counseling Could Ruin Value Proposition of PGx Testing, Insurer Says. Genomeweb: Pharmacogenomics Reporter. August 12, 2009.

The Genetics and Public Policy Center. Center publishes new survey of state false advertising laws. dnapolicy.org, August 11, 2009.

• Related: State Laws Could Cover DTC Gene Testing. GenomeWeb Daily News, August 13, 2009.

- J.O.

Genetic Testing and Privacy: Are Our Health Care Policies Adequate?

As a genetics professional who provides genetic testing, I am aware of the fact that many individuals contemplating genetic testing cite insurance and employment concerns as major reasons to forego testing. For that reason, I heaved a sigh of relief on May 21, 2008 when the Genetic Information Non-Discrimination Act (GINA) was signed in to law. First introduced in 1995, at a time when only about 300 genetic tests were currently in use and these for mainly rare diseases, it was called both forward-thinking and premature. Now hailed as the first civil rights law of the new century, GINA will prohibit group and individual health insurers from using a person’s genetic information in determining eligibility or premiums and prohibit employers from using a person’s genetic information in making employment decisions such as hiring, firing, job assignment, or other terms of employment. Guidelines for segregating genetic information from other medical records are expected to be forthcoming.

As I thought more about it, however, I realized that the world has changed rapidly in the 14 years since this bill was first introduced, and that these changes may well undermine the protections that GINA was meant to provide. I see four main threats: 1) more genetic information everywhere, 2) data expansion, 3) genome wide association studies, and 4) electronic medical records.

Under the more information heading, the terms “Genetic information” and “genetic condition” are becoming more difficult to define. We are finding that almost all illness has some genetic component such that making clear distinctions between genetic and non-genetic health information is becoming increasingly meaningless. Under the data expansion category, genetic research has shifted from diseases linked to a single gene (Huntington disease, cystic fibrosis) to more common and complex illnesses characterized by the interactions of multiple genes and environmental factors (asthma, diabetes). There are now over 1500 genetic tests in use and in the not-so-distant future, nearly all health records will include substantial genetic information. Genome Wide Association Studies (GWAS) look for single changes in the hundreds of thousands of base pairs (A,T,C,G) that make up the human genome associated with a particular illness or condition. These conditions may be as serious as breast cancer or as frivolous as what type of ear wax you are prone to develop. These tests are being aggressively marketed directly to consumers and can be ordered on line for less than $400. There is little oversight of the companies marketing these tests and as one who works in the field of genetics, it seems almost criminal to test for one mutation associated with cystic fibrosis out of the more than 1000 known CF mutations and call that information useful in the absence of extensive educational efforts. It may not be long before our patients come to our offices with their printouts from 23&Me and ask to add them to their medical record. The fourth threat may be the shift from paper-based medical records to electronic health records (EHR) with their goal of standardization, compatibility, and ease of transport. In a paper-based system, the greatest protection of individual privacy is chaos, the inability to aggregate a complete record from multiple providers over time. Comprehensive and longitudinal medical records will inevitably contain sensitive information and patients will no longer have the option of selective recall in the sense of “is that depressive episode I experienced in graduate school after being mugged really relevant information for the orthopedist performing my knee surgery twenty years later?” Electronic medical records will make it even more difficult to sequester genetic information.

One other developing trend may also play a role, the refinement of personalized medicine, the ability to target drug therapies customized to each person’s genetic makeup to both improve the effectiveness of current treatments and to reduce side effects. Pharmacogenetic testing is becoming standard practice in selecting drugs and dosages for certain cancers while toxicogenetics, the use of GWAS studies to predict how individuals may respond to certain toxins, is becoming more important in assessing both individual and public health risks. If genetic factors appear to play a role in individual and/or community resistance to flu viruses, who knows what might happen.

Technology moves rapidly while our legislature does not. A bill introduced to fix a problem in 1995 may not be as relevant or as useful in 2009. So while I am still happy that GINA was finally passed, the devil, as they say, is in the details, and it remains to be seen how much protection is actually provided for our patients and their families.

Kimberly A. Quaid, Ph.D.

Genetic Privacy: T.J. Maxx and the NIH

What do T.J. Maxx, the V.A. and NIH have in common? They have all been involved in handling personal data in such a way that individual privacy and confidentiality may have been violated. In December 2006 the financial information of over 40 million customers of T.J. Maxx and Marshall’s was accessed by a hacker potentially exposing customers to identity theft. Also in 2006, a laptop computer containing personal information including names, addresses, dates of birth and social security numbers for 38,000 veterans went missing. This past August, large amounts of aggregate human DNA data that the National Institute of Health and other groups had made open to researchers around the world was removed from public view due to privacy concerns. The reason behind this removal was a study (doi:10.1371/journal.pgen.1000167) released by the Translational Genomics Research Institute and the University of California showing that using an algorithm and a microarray a curious individual could possibly identify whether or not an individual’s DNA was in a genome wide association study (GWAS) database.

Why does this matter? NIH and other groups conducting GWA studies know that one of the core ethical components of their work, and a critical element for convincing people to participate in these studies, is being able to promise that their personal medical and genetic information will not be compromised and will never be used in such a way that might cause them harm. Being able to demonstrate, for example, that a representative of law enforcement armed with a DNA sample from a crime scene could search an existing NIH database for a sample match and be successful, undermines this promise in a way that might give us all pause. Researchers will still have access to the data, but they will now have to apply for access to the data and agree to protect the confidentiality of the data.

As researchers strive to use the information gained by the Human Genome Project for the improvement of health care and the prevention and treatment of disease, more and more of us will be asked to participate in efforts to establish enormous databases of our genotypic (DNA) and phenotypic (medical records) information. I still shop at Marshall’s, but I am not sure I will be giving my DNA anytime soon. --Kimberly A. Quaid

Resource Recommendation: NIH Points to Consider - GWAS and IRBs

Genome-Wide Association Studies (GWAS): NIH Points to Consider for IRBs and Institutions in their Review of Data Submission Plans for Institutional Certifications Under NIH's Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies (GWAS) 12 November 2007. Accessed 12 May 2008 from: http://grants.nih.gov/grants/gwas/gwas_ptc.pdf

These guidelines go beyond the regulatory requirements of 45 CFR part 46 as outlined by the OHRP's 2004 policy guidance regarding privacy and biobanks (see NOT-OD-05-020 and http://www.hhs.gov/ohrp/humansubjects/guidance/cdebiol.pdf). In addition to addressing the NIH's recent emphasis on open-access publication in the context of genomic research, this document provides a de facto outline of the many consent, privacy, and disclosure issues in biobank research. Although it is a must read for anyone conducting or reviewing NIH supported GWAS research, it is also an excellent resource to skim when thinking about the ethical issues and risks of benefit sharing and biobank research.

Genetic Research and Mental Health: Some Ethical Issues

On Monday, March 17, two Indiana University mental health researchers, Dr. John I. Nurnberger and Dr. Alexander B. Niculescu III, addressed the weekly PredictER meeting at the IU Center for Bioethics in a talk entitled: “Genome-Wide Association Studies: What Have We Learned So Far". Dr. Nurnberger is the current director of the Institute of Psychiatric Research at the IU School of Medicine and Dr. Niculescu is Assistant Professor of Psychiatry and the Director of the Laboratory of Neurophenomics. Niculescu, Nurnberger and others recently published a widely discussed [see Steve Mitchell, MSNBC, 25 Feb. 2008] blood biomarkers for mood disorders study [PMID 18301394 - PDF].

Current Challenges in Understanding and Treating Mental Health Disorders

Dr. Nurnberger (who chaired the first portion of the lecture) began the talk by outlining the prevalence of various neuropsychiatric disorders, focusing especially on Bipolar disorder. Dr. Nurnberger's discussion was supplemented by an explanation from Dr. Niculescu of some of the shortcomings that past attempts to understand the genetic links to depressive/Bipolar disorders have had. According to Dr. Niculescu, “Until recently, the lack of concerted integration between the two approaches [has]… constituted a missed opportunity to accelerate our understanding of this complex and heterogeneous group of disorders”. Simply put, mood disorders involve many, many genes, which may be present in various combinations in any one of us, and interact in ways that defy easy classification. While it is clear that individuals with certain psychiatric disorders may have certain combination more often, we are far from understanding precisely which genes are responsible for which portions of the disorders.

Dr. Niculescu then detailed two main “arms” of his research; the first involves an innovative response to the problem of how to create a sophisticated working picture of the genomics involved in mental illness. Using a technique called Convergent Functional Genomics (CFG), Dr. Niculescu's team brings data from three sources together - animal model gene expression data, human genetic linkage/association data, and finally human tissue (postmortem brain, blood) data.

The advantages of bringing these there sources of information together are manifold. Dr. Niculescu’s team has been able to cross-validate findings from other research studies. This has helped his team to “extract meaning from large datasets" and to prioritize "candidate genes, pathways and mechanisms for subsequent targeted, hypothesis-driven research”. Furthermore, as Dr. Niculescu indicates, this convergent functional genomics approach may help to deliver on one of the most exciting and elusive goals of genetic research in the area of mental health: a blood test that could identify blood biomarkers of an illness.

“PhenoChipping” and the Move Towards More Individualized Mental Health Care

As part of working towards this goal, Dr. Niculescu’s research team is implementing another innovative approach – the use of PhenoChipping. In layterms, a gene is thought to be like a “blueprint” for how something biological is built; a phenotype is the way that thing is actually built and lives, which may diverge from the plan, or may change over time according to its environment. “PhenoChipping”, thus, refers to the process of collecting mental health data from subjects using a massive inventory of cognitive and affective tools. Researchers are hoping to combine this “in vivo” data with advanced genomic data to better understand what complex interaction of genes, environments, stress, and other factors participate in these serious and highly complex neuropsychiatric disorders.

Dr. Niculescu and his team see their research as moving towards the development and implementation of more tailored, personalized treatments in psychiatry. In this more personalized medicine the patient's unique profile is the target of therapeutic interventions. Dr. Niculescu states: "We hope our work will contribute to better diagnostics, early intervention and prevention efforts, and more efficacious treatments, with reduced side-effects".

Some Ethical Questions:

This research is a rich playing field for bioethics with its intersection of illness, consent, duress, technology, and research whose implications (and even direction ) can barely be anticipated from where we stand. Some questions to consider are:

What are the ethical issues to be considered when conducting research on populations of people that are ill, and ill in a way that affects judgment?

What does consent to mental illness research mean in the absence of a cure?

What if we were able to develop a blood test that help predictive capacity for determining if someone was at risk of developing a mood disorder? What would individuals want to know, and under what circumstances?

In what ways would the ethics of this predictive, diagnostic power mimic existing models in the ethics of disclosure of illness? How, for example, would it differ from existing ethical frameworks for disclosing HIV status, terminal illness, and other conditions?

What does participation in long-term mental health genomic studies mean for participants? Can participants “withdraw” from research, and if so, what happens to their data?

– Noah Zanville

[PredictER Blog welcomes this first contribution from Noah Zanville. Noah is nursing student in the accelerated track at the Indiana University School of Nursing. He serves as a member of IU School of Nursing's Leadership Council and is a key figure working with the local chapter of National Student Nurses Association. He is currently preparing to accept a position as a Research Assistant doing applied bioethics research around end of life issues in ICU settings through the Charles Warren Fairbanks Center for Medical Ethics.

Noah earned his bachelor's in Philosophy from the University of Oregon, and is a Licensed Massage Therapist with an emphasis in Lymphedema Management, Medical Massage in acute-care settings and energy work. Noah also worked as a free-lance medical illustrator for a time.]

Korea’s NIH Initiates Genome-Wide Association Study

From GEN News Highlights, Jun 12 2007.

Republic of Korea's NIH (KNIH) and Center for Disease Control and Prevention will use the Affymetrix Genome-Wide Human SNP Array 5.0 for the Korean Association REsource (KARE) project. This genome-wide association study is designed to identify the genetic causes of lifestyle-related complex diseases that are prevalent in Korea.

PredictER Note: SEE related content, Michael White's blog entry reviewing the efficacy of Genome Wide Association Studies (GWAS); "Genome-wide Association Studies - Are the Long-Promised Benefits of the Human Genome Project on the Horizon?" Adaptive Complexity, June 13, 2007.

Presentations from the NHGRI Science Reporters’ Seminar on Genome-Wide Association Studies

from National Humane Genome Research Institute (NHGRI). Retrieved 14 June 2007 from http://genome.gov/25521070

NHGRI Holds Science Reporters' Seminar on Genome-Wide Association Studies

Bethesda, Md., May 1, 2007 - The National Human Genome Research Institute (NHGRI) offered a seminar on Genome-Wide Association Studies (GWAS) to leading science reporters from major media around the United States. Genome-Wide Association Studies have been possible only in the last two years since the completion of the International HapMap Project in October 2005 and the development of several new technology platforms that have dramatically reduced the cost of genotyping, a kind of scan across a person's entire genome that seeks out genetic variation. Now, numerous research teams will be reporting results on common disease, ranging from heart disease to cancer to mental illnesses and diabetes.

In the seminar, NHGRI experts in this new field explain how the science works, how it will speed up the understanding of the genetics of common diseases, and how that will lead to the development of new diagnostics, preventives and therapeutics.

PredictER Note:

Site includes links to video and slide presentations from the conference:

Welcome and Introduction. Francis Collins, M.D., Ph.D.; Director, National Human Genome Research Institute

Human Heredity and Environment: Nature and Nurture. Emily Harris, M.P.H., Ph.D.; Epidemiologist, Office of Population Genomics

Genetic Variation. Larry Brody, Ph.D.; Senior Investigator, Genome Technology Branch.

Genome-Wide Association Studies. Teri Manolio, M.D., Ph.D.; Senior Advisor to the Director for Population Genomics

Common Disease Findings. Francis Collins, M.D., Ph.D.; Director, National Human Genome Research Institute

Genetic Influence on Human Traits and Behaviors. Elaine Ostrander, Ph.D.; Chief and Senior Investigator, Cancer Genetics Branch

Genetics and Race. Vence Bonham, J.D.; Senior Advisor to the Director on Societal Implications of Genomics