Nuffield Council Reviews DTC Genetic Testing

The Nuffield Council on Bioethics recently released the results of a two year study: Medical profiling and online medicine: the ethics of 'personalised healthcare' in a consumer age (2010). The report devotes chapters to six "case studies" (these are not formal case studies, but rather topics for investigation), all are relevant to the ethical development and delivery of predictive medicine. The six case studies address: online health information, online personal health records, online purchasing of pharmaceuticals, telemedicine, personal genetic profiling for disease susceptibility, and direct-to-consumer body imaging.

However, the chapter on direct-to-consumer (DTC) genetic testing, 9. Personal genetic profiling for disease susceptibility, will be of particular interest to readers in the States. Three of the big names in DTC genomics are U.S. companies (Navigenics, 23andMe, and Pathway Genomics) and, given the price tag for services, much of the consumers are in the States as well. In general, the Council cautions that DTC genetic testing lacks a sufficient evidence base for reliable clinical use and that consumers should think carefully about the risks. Nevertheless, the workgroup does not oppose the market for DTC genetic testing, but rather advices companies to provide greater transparency regarding the evidence and the potential harms. On the regulatory front, the report proposes prohibiting the market for tests with no proven clinical utility. See 9.45:

We recommend that responsible authorities pay more attention to whether genetic test providers are making clinical claims for their products, even if implied rather than explicit (such as in their ‘customers’ testimonials’). If so, they should ask for evidence to be supplied. We direct this recommendation to authorities responsible for pre-market review and advertising standards, including the Medicines and Healthcare products Regulatory Agency and the Advertising Standards Authority in the UK.

The council also calls for government (UK) websites to publish the risks and limitations of DTC genetics, for restricting pediatric DTC genetic services, and for programs to educate healthcare providers who may need to discuss DTC genetic test results with patients.

In addition to the six "case studies" the report also provides a chapter devoted to ethical values the workgroup identified as well as the process of ethical reasoning it employed. The workgroup the following ethical values to consider:

1. The value of safeguarding private information;

2. The value of individuals being able to pursue their own interests in their own way;

3. The value of efforts by the state to reduce harm;

4. The value of using public resources efficiently and fairly;

5. Sharing risks, protecting the vulnerable: the value of social solidarity.

These values, of course, are often in conflict with each other. Thus, the workgroup employed a practical approach (not to resolve) but to "soften" conflicts, see 3.18:

[T]he approach we follow in this report is not so much to attempt to solve the dilemmas but to propose forms of oversight and voluntary conduct so that society can manage its way around them and reduce the conflict while gaining general assent. This approach means trying to accommodate as many as possible of the different values we have identified without giving one absolute priority over another.

I think this is a pragmatic approach, but (perhaps) too obvious to bear replicating. It might have been more interesting to learn how the workgroup identified the five ethical values it employed.

In addition to its well-considered case studies, and explained ethics practice, the report serves as a valuable review (with an emphasis on the issues in the UK) of the literature on the ethics of personalized and genomic medicine. It can be downloaded at no cost from the Council's website: http://www.nuffieldbioethics.org/

Other Predictive Health Ethics News

Tara Parker-Pope. Taking genetic history to the grave. Well (NYT Blog). October 28, 2010.

Rita Rubin. Most doctors are behind the learning curve on genetic tests. USA Today. October 25, 2010.

Laurie Udesky. The ethics of direct-to-consumer genetic testing. The Lancet. October 23, 2010.

Jessica Reaves. Stem Cell Research Skirts Hurdles, but Raises Ethics Issues, Too. The New York Times. October 22, 2010.

Philippa Brice. Loss of UK genetics public bodies confirmed. PHG Foundation News. October 15, 2010.

Experts warn about genetic tests. Reuters. October 12, 2010.

Matt Ridley. The Failed Promise of Genomics. The Wall Street Journal. October 9, 2010.

Amy Harmon. Stem Cells in Court, Scientists Fear for Careers. The New York Times. October 6, 2010.

Josephine Johnston. America’s Stem Cell Mess. The Scientist. October 1, 2010.

Dan Vorhaus. HHS Pulls the Plug on Genetics Advisory Committee. Genomics Law Report. September 23, 2010.

-- 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.

Personalized Medicine: PredictER Collaborator Featured in NY Times

David A Flockhart, MD, PhD, Division Chief of the IU Department of Medicine’s Division of Clinical Pharmacology and PredictER Collaborator, was featured in a December 29th New York Times article that is part of a compelling series examining steps taken toward medicine based on evidence. The article, Patient’s DNA May Be Signal to Tailor Medicine, provides a highly readable overview of personalized medicine, illustrates the field’s inherent potential to increase positive outcomes and decrease costs, and then discusses some of the conundrums that genetically-tailored medicine presents. The author, Andrew Pollack, uses the outcomes of Flockhart’s extensive tamoxifen research to aptly illustrate the medical promise of genetic testing and its broader implications. Flockhart’s research demonstrates that a particular enzyme, CYP2D6, is responsible for converting tamoxifen into a different substance, called endoxifen, which is then directly responsible for fighting breast cancer. The CYP2D6 gene, however, varies between people such that the mechanism is inactive in about 7% of the population, and only moderately active in 20-40%. As the article points out, most patients are now treated with a more expensive class of drugs that demonstrated greater efficacy in clinical trials conducted before the role of CYP2D6 was fully understood. For those women with active CYP2D6, however, tamoxifen may well be the better alternative for the patient, both medically and economically. Genetic testing to determine gene activity in this scenario may therefore have vast economic implications for the pharmaceutical industry.

Amy Lewis Gilbert

Genetic Testing and Personalized Drugs: PredictER at Spirit and Place

As part of the 2008 Spirit & Place Festival, a panel of experts from the Indiana University Center for Bioethics and the Indiana University School of Medicine will join together to illustrate the complex intersection of ethics, medicine and science. Dr. Eric M. Meslin, director of the Center for Bioethics; Dr. Kimberly A. Quaid, professor of medical and molecular genetics; and Dr. David Flockhart, chief of the division of clinical pharmacology, will present Imagining Our Medical Future: The Ethics of Predictive Genetic Testing and the Search for Personalized Drugs this Sunday, November 9th, 2:00-4:00 p.m. at the Indiana Medical History Museum, 3045 W. Vermont Street, Indianapolis. Free tours of the museum will be available both before and after the panel discussion. More information regarding the Spirit & Place Festival, which is runs now through November 16th, is available at www.spiritandplace.org - ALG

The Best Predictive Health Ethics Blogs - June 2008

California and Direct-to-Consumer Genetic Testing:

California's decision to send cease-and-desist letters to thirteen direct-to-consumer genetic testing companies (including 23andME, deCODEme, Knome, and Navigenics) ignited a blogging wild-fire of mostly outraged responses. Some of the more widely read expressions of protest were blogged at Wired Science and include Thomas Goetz's much-echoed Attention, California Health Dept.: My DNA Is My Data (17 June 2008). For an alternative reaction see Steve Murphy's posts on the topic at Gene Sherpa, which include: Do you hear that sound Mr Anderson? (15 June 2008), A$$ Kicking (17 June 2008), and R'Uh-R'Oh Shaggy!!! (17 June 2008). Although many of the replies to Murphy's posts offer only more expressions of outrage, Daniel MacArthur at Genetic Future engages Murphy in a thoughtful exchange beginning with California cracks down on genetic testing companies (15 June 2008) and Cat-fight over California (18 June 2008). Finally, for a good overview of the news and blogging on the subject, see Blaine Bettinger's recent post The Genetic Mess in California - A Round-Up, and My Thoughts (30 June 2008) at The Genetic Genealogist.

Employee Wellness

Matt Mealiffe of DNA and You writes in response to the news that Japan will require companies and local governments to "measure the waistlines of Japanese people between the ages of 40 and 74 as part of their annual checkups" with the standard of "33.5 inches for men and 35.4 inches for women" (see Norimitsu Onishi, Japan, Seeking Trim Waists, Measures Millions. The New York Times. 13 June 2008). In Mealiffe's assessment (14 June 2008), mandatory waistline measurement is "bold social policy" which may be, however, genetic discrimination.

In an unrelated post on a similar topic, Jane Sarasohn-Kahn of Health Populi reports employee attitudes regarding the privacy risks of employers' wellness programs. Writing in Is worker wellness a privacy issue? (5 June 2008), Sarasohn-Kahn summarizes the findings of a recent report: "Employees are concerned that this information could be used to reduce benefits or for even more egregious purposes". An overview of the findings, "Health and Wellness: the shift from managing illness to promoting health" is available from the Center for Studying Health System Change [PDF].

Law & Policy

Andrew W. Torrance of BioLaw: Law and the Life Sciences reflects on the sometimes presumed amoral status of patent law in U.S. – a status that is not presumed in Europe. In Patently Immoral Genes (2 June 2008), Torrance shares the recent, related work of the European Society of Human Genetics ("ESHG") which "has issued recommendations that would severely limit patents on genes in the European Patent Office (EPO) and member states of the EPC." According to Torrance, "the ESHG recommends that the EPO establish an 'ethics committee' to police the patentability of controversial technological innovations". He believes that this news may be of interest to policy makers in the States, including: California Democrat, Xavier Becerra, a sponsor of the "Genomic Research and Accessibility Act" (H.R.-977 – Thomas | GovTrack.us).

Nick Agar writes at What Sorts of People on a report by The Bioethics Council of New Zealand on the completion of its program Who gets born? Pre-birth testing. The report responds to the New Zealand government's decision to fund pre-implantation genetic diagnosis for couples with a high risk of conceiving a child with a genetic disorder. In NZ bioethics council (27 June 2008), Agar notes that "the emphasis is very much on facilitating parental choice, with health professionals given the role of supplying parents with the information they need to make choices consistent with their values". He observes that the Council made a deliberate effort to solicit participation from a wide range of "interested parties", but cautions that there may be "a bit of fallacy of bureaucratic representativeness here – if a committee’s composition approximately matches the representation of various communities in the general population then its pronouncements must be representative of the viewpoints of those different communities".

Personalized Medicine

Reflecting, in part, on the prevalence of "Personalize Medicine" in the recent 2008 BIO Convention, Jennifer Miller at Bioethics International defines the topic and introduces some of the ethical and legal issues. She identifies six ethical issues in Personalized medicine: an introduction, its promises and the ethics (26 June 2008):

(1) just access to, allocation and application of the new technologies, (2) privacy concerns, (3) respecting parties’ autonomy, (4) obtaining quality informed consents, (5) intellectual property rights, particularly in connection with bio-banking, (6) overall resource allocation and prioritization questions ….

Reviews

Bonnie Green, writing for BioethicsBytes (17 June 2008), reviews "An Adventure into Ourselves", the third episode of a four-part television series entitled DNA: The Human Race (Channel 4, 2003). [BioethicsBytes hosts and reviews resources for ethics education. The project aims "to assist in the teaching of bioethics, with particular emphasis on multimedia materials (film, TV, streamed media) as case studies".] Green's thorough review of "An Adventure into Ourselves" marks interesting quotations and highlights the social and political context of the Human Genome Project (HGP). She observes that the series and the episode form "an excellent basis for teaching both the science and bioethics of the HGP and large scale sociotechnical projects". The post also includes YouTube footage from related programming about the X-Prize.

Writing for Gene Expression, "Herrick" reviews Heredity and Hope: The Case for Genetic Screening, by Ruth Schwartz Cowan (Harvard University Press: 2008. 270 pp. $27.95, £18.95). This blogger points to three aspects of Cowan's book on genetic screening. In Heredity and Hope by Ruth Schwartz Cowan (11 June 2008), "Herrick" observes that Cowan distinguishes contemporary genetic medicine from mid-20th century eugenics by 1) showing that "genetic screening is a bottom-up social phenomenon, not a top-down mandate", 2) highlighting the "pro-natalist" aspects of contemporary genetic screening, and 3) sharing happy-ending stories about the proper use of this technology. In conclusion, "Herrick" observes:

Functionally, Cowan does the same thing for genetic screening that The New Republic did for tough-on-crime policies in the 80's and 90's: Cowan does some liberal hand-wringing while telling the reader that no, you're not becoming a Brownshirt if you agree to an amnio.

The BiDiL Debate: Can "race" serve as a proxy for groups with shared "genetic" characteristics?

Following the debate surrounding the FDA's 2005 approval of BiDiL – a drug to be marketed to treat African-Americans at risk for heart failure – David e. Winickoff and Osagie K. Obasogie propose regulatory policy for future race-specific drug development. Writing in a letter published in Trends in Pharmacological Sciences [Race-specific drugs: regulatory trends and public policy. 2008 Jun;29(6):277-9. Epub 2008 Apr 29 | PMID: 18453000 - CiteULike (excerpt)], the authors argue: "race-specific indications should be rejected unless clinical trials can demonstrate convincingly that the drugs are both better than existing treatments for a specific group and no better than existing treatments for non-specified groups". They conclude that these enhanced regulations might help to reduce health disparities while protecting groups from market exploitation: "Race can be used as a proxy for the group most likely to benefit from a drug as long as the effect is not to deny others valid treatments". In other words, "Pharmaceutical science and biomedicine most certainly should not be colorblind. But they also must not be 'color-struck'".

Unlike one's genetic information, racial identity is a social-construct – so, using race as a proxy for individuals with common genetic characteristics is a messy and controversial process. In this case, would it make sense at all to say: genome-specific "indications should be rejected unless clinical trials can demonstrate convincingly that the drugs are both better than existing treatments for a specific group and no better than existing treatments for non-specified groups"?

Would such a standard be useful or does it merely re-state the obvious? – J.O.

Curating Your Personal Genome?

When a member of the PGP-10 and an investor in 23andMe writes about curating one's online, personal data, a lot of people listen. Unfortunately, Esther Dyson (writing in MIT's Technology Review) does not mention the decision to share medical information or how she plans to curate her own genomic data online. Dyson rightly notes that "current website 'privacy' policies don't suffice. They're full of abstractions, euphemisms, and generalities, such as, 'We may, at any point in time, provide certain Specified Information to selected Marketing Partners ... .'" She appears to favor a complex, itemized consent policy, one that would allow users to opt in or out of sharing specific categories of information (user name, address, credit history, etc.) with a list of potential users (advertisers and other companies).

Imagine a similar consent for medical records sharing. For example, could someone like Esther consent to share her genome with a 23andMe social network, but not with researchers in this network? Or, perhaps, Esther could chose to share some of her genomic information, but not all of it. Then, again, maybe Esther would be willing to share her prescription history with an academic researcher, but not with pharmaceutical companies. The options could go on and on, resulting in an increasing complex array of choices.

Esther Dyson is obviously a very sophisticated information agent, but (as the opportunity to share medical information online increases) will the average user and patient be prepared to make informed decisions about the risks and benefits of participating? - J.O.

Navigenics Enters Personal Genomics Game ... Meanwhile: "What's a SNP?"

On April 8th, Navigenics announced it will provide genomic testing services to the general public, yet, creating additional competition among other genetic health startup companies such as deCODEme and 23andMe. These businesses are drawing attention by allowing ordinary people to see their genetic makeup and by providing services to help understand their risk for common conditions.

For an initial fee of $2500, Navigenics’ personalized medicine package includes genotyping for 18 listed medical conditions such as Alzheimer’s disease, glaucoma, colon cancer, lupus, breast cancer, prostate cancer, and Crohn’s disease. Saliva, instead of blood, is collected for the genome scan as a less invasive and less hazardous approach. Within three weeks, Navigenics promises to deliver your risk assessment report electronically and provides genetic counseling over the telephone to educate customers on their genetic predispositions and to encourage them to take preventive measures.

The personal genomics industry is growing and potential consumers have choices. For example, 23andMe lets customers see their entire genetic profile of more than 500,000 single nucleotide polymorphisms (SNPs) while Navigenics limits customers to 18 selected conditions, even though it uses a 1 million SNP chip. On the other hand, Navigenics promises the customer access to future technology for an annual fee of $250. Customers’ spit samples are frozen, stored, and re-tested as new associations with SNPs are found.

Hoping to set industry standards, Navigenics proposed 10 criteria for performance, quality, and service for personal genomic services:

1. Validity
2. Accuracy and quality
3. Clinical relevance
4. Actionability
5. Access to genetic counseling
6. Security and Privacy
7. Ownership of genetic information
8. Physician education and engagement
9. Transparency
10. Measurement

With the evolution of personalized medicine and genetic profiling, consumers have more information in their hands. New research initiatives are on the move to understand how consumers act upon this information (i.e. ignore health risks or needlessly worry about slight risks). Navigenics has plans to support future health outcome studies and has recently joined forces with the Mayo Clinic to measure the impact genetic information has on behaviors.

It will be interesting to see whether The Personalized Medicine Coalition adopts or modifies Navigenics standards. Also interesting will be the response from the medical community to risk assessment reports generated by personal genomic businesses such as Navigenics, 23andMe, and deCODEme.

What could be better than knowing your own DNA? This genomic revolution sounds almost too good to be true. Dr. Eric Topol, cardiologist at the Scripps Clinic (ironically a collaborator with Navigenics), listed his comments (December 2007) in an editorial for The Wall Street Journal. Topol presumes it is too soon to tell whether having your genome scanned can be good for your health because there are so many unidentified genes associated with disease risk. He also wonders, as do I, how personal genomics will impact the medical community. His example . . . "When a consumer arrives in his or her doctor’s office to get help in interpreting the genomic data, the doctor is likely to respond: What’s a SNP?" – Katie Carr

[Katie Carr is a graduate student in public health at Indiana University-Purdue University, Indianapolis (IUPUI). In addition to taking classes in bioethics at the IU Center for Bioethics, Katie is working with us to develop an ethical plan for pandemic influenza response.]

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

Genealogy, Genetic Medicine and Getting the Story Straight

What is the promise of personalized medicine and predictive health? Here's a rough description: physicians will know more about individual patients and will therefore be better equipped to provide care. But will it be so simple? In any field, the acquisition of more information, even accurate information, does not necessarily lead to successful application. So, let's say we all buy a test from 23andMe or deCode or Navigenics or any of the growing list of direct-to-consumer genomics company ... and we unpack every last bit and byte of our genetic data, will the world be a healthier place? Or, let's say, just a few of us fork over the $1000 to have our genomic fortunes told … are we really ready for the complications that this information may bring?

If the practice of genetic genealogy is any indication, the future of medicine in the genomic era will be suffused with complications. Nancy Berlinger, of Bioethics Forum, provides an engaging and insightful account of a few of these in "And I am Marie of Romania: Genetics, Genealogy, and the Ethics of Storytelling". Berlinger adds to the ongoing commentary on the new Henry Louis Gates, Jr. venture, AfricanDNA. Gates started this venture, in part, because of frustrations with inaccurate and misleading genetic genealogy results. As Berlinger writes, the misinterpretation (that Gates possesses a genetic link to those once living in the ancient North African kingdom of Nubia, and not, as it turns out, to a less impressive European "servant" in the American colonies) might have been the result of poor science, but also, might be attributed to "wish fulfillment on the part of geneticists and their clients".

To the Gates story, Berlinger contributes related accounts of individuals receiving, accurate, but potentially unwelcome, genealogical information. While America still struggles with its racist inheritance, individuals like Bliss Broyard struggle with new found genealogical information (see her new memoir, One Drop: My Father’s Hidden Life — A Story of Race and Family Secrets). Every one has family secrets--information we are not privy to at the moment--and (as Matt Mealiffe reminds us in Who's Your Daddy?) there's no reason to believe that all or even most of these secrets are about race. Clearly, genetic genealogy (as Blaine Bettinger often notes) is no simple task--will personalized, genetic medicine be any easier? Who will hold and who will expose the secrets in your genome? Is it possible, just maybe, that a one or two of the most enthusiastic, early adopters of personalized medicine will discover a few things they'll wish they'd never known? - J.O.

Predictive Health Research: What Isn't It?

If you're a regular reader of this blog, if you receive PredictER News Brief, if you have attended any PredictER event; you've probably encountered definitions of "predictive health research". But, let's pretend you're not a regular PredictER Blog reader; imagine that! You might wonder … What's the big deal; aren't all medical professionals predicting health outcomes? Isn't most medical research conducted with the hope of better predicting health outcomes? Well, you're not alone. These are questions I regularly entertain when updating PredictER's shared headlines (see the panel on the right) or when adding items to PredictER's del.icio.us and CiteULike accounts. In fact, two recent news items seemed to be begging to stretch the scope beyond the typically featured genetic and neuroimaging research. First, on the 30^th of October, The Washington Post reported "Quality of Life Predicts Lung Cancer Survival". The story relays the news of recent cancer research findings and quotes the lead author, Dr. Nicos Nicolaou of the Fox Chase Cancer Center in Philadelphia:

"In the past, we've considered the stage of disease or tumor size along with other empirical data to predict how long a patient will survive, but now we know quality of life is a critical factor in determining survival".

The second story, also relaying research news on "survival" factors, appeared Wednesday in MedPage Today: "Mathematical Index Simplifies Survival Prediction After Liver Grafts". In the November 7^th report, Judith Groch writes:

The researchers [Michael L. Volk and colleagues at the University of Michigan] said that the modified comorbidity index predicted liver transplant survival as well or better than other available models that typically use recipient characteristics such as age, race, BMI, and etiology of liver disease. … Until now, "we have considered comorbidities in an informal way when deciding whether to put patients on the list for transplant, but nobody has ever quantified the impact of comorbidities on post-transplant survival," Dr. Volk said.

Sounds "predictive" to me, but is it relevant to PredictER? I can't say "no", but I have to admit that PredictER Blog has focused on research emphasizing long-term prediction … tests and methods revealing disease years (if not decades) prior to the onset of symptoms. This "predictive" research often requires the latest developments in research knowledge and technology; it also introduces a new emphasis on some familiar ethical and social issues. When research requires biobanks and databases for the collection of tissue samples and genetic data for potentially long-term and unexpected use, the task of assuring subject privacy, dignity, and autonomy faces new challenges. These challenges are multiplied when biobanks are coupled with longitudinal access to personal medical records. Thus, while reserving the opportunity to be inclusive, the interests of PredictER Blog can be distinguished from the "predictive" aspects of all biomedical research (exemplified by the Nicolaou and Volk studies) by a measure of degrees. PredictER Blog is interested in research aims marked by dramatic increase in the power and accuracy of health "prediction", the requisite ethical protections, and the much anticipated benefits ... a more personal "personalized medicine".

Related research:

Volk ML, Hernandez JC, Lok AS, Marrero JA. 2007. Modified Charlson Comorbidity Index for predicting survival after liver transplantation. Liver Transplantation. Volume 13, Issue 11 , Pages 1515 - 1520. [doi: 10.1002/lt.21172]

Nicolaou N, Moughan J, Sarna L, Langer C, Werner-Wasik M, Komaki R, Machtay M, Wasserman T, Bruner D, Movsas B. 2007. Quality of Life (QOL) Supercedes the Classic Predictors of Survival in Locally Advanced Non-Small Cell Lung Cancer (NSCLC): An Analysis of Radiation Therapy Oncology Group (RTOG) 9801. International Journal of Radiation Oncology, Biology, Physics. Volume 69, Issue 3, Pages S58-S59. [doi:10.1016/j.ijrobp.2007.07.107]

Web 2.0 + Medicine = Medicine 2.0: Featured Blogs

ScienceRoll and Medicine 2.0

Readers interested in casual discussions on the future of medicine at the cross-roads of genetics research, electronic medical records, and the internet will find plenty to read in recent blog entries using the terms "Medicine 2.0" or "Health 2.0". Advocates of the subject, include Bertalan Meskó, a medical student at the University of Debrecen (Hungary). Meskó, who monitors and writes about the topic in his blog ScienceRoll, holds that "the new generation of web services, will [play] (and already is playing) ... an important role in the future of medicine. These web tools, expert-based community sites, medical blogs and wikis can ease the work of physicians, scientists, medical students [and] ... medical librarians". In addition to regular posts on his blog, Meskó also edits a weekly blog carnival (an index or review of blog entries) on the subject, entitled Medicine 2.0. Mesko's ScienceRoll also contributes entries on genomics, clinical genetics, genetic testing, and personalized medicine.

"Medical Ethics 2.0"

Science Roll, July 19, 2007 and Medicine 2.0, hosted recently by J.C. Jones at HealthLine Connect were among several blogs citing "Medical Ethics 2.0", published July 16th by Jason Bobe at The Personal Genome . [Others citing Bobe include: Philosophy and Bioethics and The CEP Library.] Bobe discusses the possibility that future users of online genealogy services may begin to add medical information to their family trees. Following his review of the BMJ “Head-to-Head” feature: “Should families own genetic information?” [BMJ 2007;335:22 (7 July), doi:10.1136/bmj.39252.386030], he questions how user-generated genetic information and Web 2.0 technologies would complicate the ethical problems of privacy and disclosure.

Medical Ethics 3.0?

In "Health care eyes Web 3.0" (Government Health IT, 16 July 2006), Brian Robinson reports on developing Semantic Web technologies and their anticipated impact on the medical formatics and health care provision. The Semantic Web uses Resource Description Framework (RDF), Web Ontology Language, and other ontologies to "ascribe meaning to data depending on the context in which it is used". The Semantic Web is expected to provide, for example, the ability to "identify data related to age, weight and diseases, and ... then deliver that data based on the context of a query". Projects in development include: rules-based diagnostic decision-support systems for Partners HealthCare System (Boston) and a public health surveillance system under the direction of Parsa Mirhaji at the University of Texas Health Science Center at Houston.

In addition to Mirhaji, comments are provided from Dean Giustini (Biomedical Branch Library, University of British Columbia), Vipul Kashyap (Partners HealthCare), and Bob Shimp (Oracle's Global Technology Business Unit). The story does not, however, explore the social and ethical implications of the Semantic Web for medical research.