Not-too-Direct Commercialization of Direct-to-Consumer Genetic Testing

  • Navigenics-and-Me: my “genetic selfie” for personalized medicine 
  • 23andMe: a widely watched and hotly debated story

When working at Life Technologies in 2009, I took advantage of the company’s health-oriented initiative to generously subsidize employees’ genetic analysis by Navigenics, which at the time was the first provider of direct-to-consumer (DTC) SNP-based genetic testing and medical counseling. Since then, there has been explosive interest—and intense debate—about a person’s “right” to their genetic information and the pros and cons of DTC genetic testing, as well as considerable corporate maneuvering in this marketplace, such as Life Technologies acquisition of Navigenics in 2012.

In addition to my being both a “consumer” and “technophile” of nucleic acid-based DTC genetic testing, a number of recent events triggered my decision to write this post. On the technology side was the sad passage last November of Frederick Sanger, winner of two Nobel Prizes and “father” of his eponymous sequencing method that provided the foundation for sequencing the human genome some ten years ago. Also, last November the FDA granted marketing authorization for the first high-throughput (next-generation) genomic sequencer, Illumina’s MiSeqDx, which will allow development and use of innumerable new genome-based tests, as reported in the New England Journal of Medicine. On the consumer side was the “upbeat” Consumer Genetics Conference held in September 2013 that, only two months later, was followed only by the FDA’s “bombshell” cease-and-desist letter to 23andMe, which is perhaps the most widely watched DTC genetic-testing company.

So, with all of these events swirling around in my brain, I decided to offer the following comments on what Navigenics did and found for me, several aspects related to 23andMe, and an outline of some of the other corporate players in the rapidly expanding, new world of advanced genetic-testing that aims to go far beyond all current FDA-approved nucleic acid-based tests.

“Navigenics and Me”

david

David B. Agus, M.D.

dietrich

Dietrich Stephan, Ph.D.

Before the “me” part, here’s the backstory (detailed elsewhere) on Navigenics. The company was founded in 2006 by David B. Agus, M.D., a prostate cancer specialist and Professor of Medicine and Engineering at the University of Southern California, and Dietrich Stephan, Ph.D., a human geneticist and Chairman, Department of Human Genetics at University of Pittsburgh. Navigenics began selling its genetic testing services in 2008 based on SNP analysis to assess risk for a variety of common health conditions. The company also launched an online portal allowing doctors to access the genomic information of consenting patients. The portal allows the physician to integrate patients’ genetic information into personalized health plans designed to help early diagnosis or prevention of a number of health conditions.

In June 2008, California health regulators sent cease-and-desist letters to Navigenics and 12 other genetic testing firms, including 23andMe. The state regulators asked the companies to prove a physician was involved in the ordering of each test and that state clinical laboratory licensing requirements were being fulfilled. The controversy sparked a flurry of interest in the relatively new field, as well as a number of media articles, including an opinion piece on Wired.com entitled Attention, California Health Dept.: My DNA Is My Data. Two months later Navigenics and 23andMe received state licenses allowing the companies to continue to do business in California.

In July 2012, genetic analysis tools-provider Life Technologies announced its acquisition of Navigenics, with Ronnie Andrews, president of Medical Sciences at Life Technologies, commenting that “[t]he advent of personalized medicine will require a combination of technologies and informatics focused on delivering relevant information to the treating physician. Navigenics has pioneered the synthesis and communication of complex genomic information, and we will now pivot the company’s effort to date and focus on becoming a comprehensive provider of technology and informatics to pathologists and oncologists worldwide.”

I was unable to find more recent or specific information about this acquisition, perhaps largely due to the fact that Life Technologies itself is in the process of being acquired by Thermo Fisher Scientific, so things are in flux. However, Thermo Chief Executive Marc Casper said in a press release that “advanced genetic testing was an important field going forward, and his company wanted to get into it as an industry leader” through the acquisition of Life Technologies. Stay tuned.

Now for the “me” part.  I’ll start with some basic info about what the past Navigenics methodology involved, what’s provided, and an important disclaimer, taken from my Navigenics Health Compass Report:

  • DNA is collected via a saliva sample, and the DNA is probed for appropriate SNP markers in a CLIA-certified lab.
  • Included SNPs have been reliably shown in cited publications to be associated with diseases.
  • Presence of such markers does not mean that the individual will definitely develop a given health condition, but can raise risk, especially if other lifestyle or environmental risk factors are present.
  • Complex results are analyzed with mathematical formulae to calculate an individual’s risk for the conditions and medication outcomes.
  • The result is an estimate of the individual’s own lifetime risk, compared with the population average, and is provided in a report that is easily understood, but extensively documented.
  • Navigenics emphasizes that these results are “not a diagnostic test”, but rather “highlight genetic predisposition to common conditions and medication outcomes, so that prevention measures may be taken, early diagnosis made, or appropriate medications chosen.”

My Genetic Selfie 

This hopefully not too trendy section heading is just another way of referring to my Navigenics Health Conditions Results, which are cut-and-pasted from my Navigenics Health Compass Report and given below in alphabetical order. Based on my “flagged” (in orange) risk results, I obviously did homework on Graves’ disease, which is the most common type of hyperthyroidism (overactive thyroid) that is more common in women than in men. People with Graves’ disease usually have lower than normal levels of thyroid-stimulating hormone—mine is currently normal. As for risk of heart attack, I’m following my doctor’s advice for dealing with my elevated blood pressure. Interestingly, I’m not (yet) lactose intolerant, but do have some arthritic symptoms and use occasional medication for psoriasis. As for obesity, I exercise regularly and (try to) avoid fattening foods.

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Regarding eight medications assessed, I learned that I have “moderate risk” of severe reaction to Irinotecan (Camptosar®), which is used to treat cancers—mainly colon cancer—and works by preventing DNA from unwinding by inhibition of topoisomerase.

As for assessed medication effectiveness, my results tabulated below are self-explanatory, and prompted me to consider wearing a medications bracelet regarding Warfarin.

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By the way, I thought it was quite apropos for Dr. Agus, who co-founded Navigenics, to share some of his Navigenics Health Compass Report on his website that you can view here, as well as check out his two books entitled A Short Guide to a Long Life and The End of Illness.

You may not like what your “genetic selfie” tells you (taken from dukehealth.org via Bing Images).

You may not like what your “genetic selfie” tells you (taken from dukehealth.org via Bing Images).

What’s with 23andMe?

The short backstory on 23andMe is that—like Navigenics—it too was founded in 2006, by Anne E. Wojcicki and Linda Avey. It began offering services about a year or so later, with the stated goal of “empowering individuals to access, explore, share, and better understand their genetic information, making use of recent advances in DNA analysis technologies and proprietary web-based software tools.” Just as Navigenics and Life Technologies have connected, so to speak, 23andMe partnered with Illumina—even earlier—to leverage the latter’s SNP genotyping platform technology, as discussed elsewhere.

Anne E. Wojcicki

Anne E. Wojcicki

 Linda Avey

Linda Avey

Fast-forward to December 2013 and these snippets from a Nature Editorial entitled—cleverly—The FDA and me, wherein I’ve added bolding for emphasis of certain key perspectives with which I agree.

“Late last month, US regulators dropped a bombshell on…23andMe in an exasperated cease-and-desist letter that prompted a fast and contrite response from the company—and a flurry of criticism of both parties among scientists and self-styled Health 2.0 activists who advocate the use of Internet tools in medicine.

The company has walked a fine line between promising that this activity will revolutionize medicine and averring that it is not actually medical at all, in an attempt to simultaneously lure in customers and avoid the need to conform to medical regulations.

The US Food and Drug Administration (FDA) has now called 23andMe’s bluff, complaining that the company has ‘not completed’ some studies that would prove the soundness of its methods and ‘not even started’ others; that 23andMe has shunned communication with the FDA since May; and that the company has launched a large advertising campaign without getting marketing approval. The agency demanded that 23andMe stop marketing its testing kit until it received proper authorization.

But the big question is not whether regulators will stop people from understanding their own DNA—they cannot. The question is whether such understanding has reached the point at which companies can exploit it, and if so, how to protect their customers. Part of answering that question is determining whether a company’s claim is true. This is what the FDA is trying to do, and until earlier this year, it seemed that 23andMe was happy to aid that mission—FDA approval, after all, would dispel worrying chatter about whether regulators would ultimately shut the company down. Mainstream biotechnology companies learned a long time ago that it pays to play nice with regulators.

Consumer demand is low in part because genetic tests on healthy people still cannot be relied on to produce consistent predictions about medical risks. Customers of 23andMe have detailed how the service variously provides lifesaving information and misleading results. This is simply the state of the science today. Silicon Valley ‘health disrupters’ who plan to revolutionize health care…like to think that they can apply their successful data-mining strategies to medicine, but it turns out that biology is more complicated than they perhaps first assumed.

No one should be fooled into thinking that direct-to-consumer genetic testing is doomed to fail. The science is moving so much faster than medical education that motivated and self-taught laypersons can learn and understand just as much about their genetic medical risks as can their doctors. Indeed, there are already public crowd-sourced tools that customers can use to interpret their genetic data for free. So even if regulators or doctors want to, they will not be able to stand between ordinary people and their DNA for very long.

In the meantime, it seems short-sighted for companies to rebuff regulators. If it is too onerous to prove the accuracy of the information they offer, they should not be selling this information in the first place. And if they turn up their noses at regulators, they may run afoul of an even more powerful force: the US system of civil litigation. Consumers are already joining class-action lawsuits alleging that 23andMe is selling misleading information. Such suits are much more effective than anything the government can do to get companies to change their practices.

To its credit, 23andMe seems to have learned this: on 26 November, [its CEO] acknowledged in a blog post both that the ‘FDA needs to be convinced of the quality of our data’ and that ‘we are behind schedule with our responses’ to the agency. The company has also stopped marketing.

It seems, then, that 23andMe’s experience with the FDA is less about the growing pains of a new industry than about affirming a principle—the need for truth in advertising—that is as old as business itself.” 

As mentioned in the above Editorial, the internet is chock full of dueling opinions about FDA v. 23andMe, and includes this poll in GenomeWeb that clearly reflects mixed and widely varying public thought on this matter:

Question: Do you think the FDA was right to send a warning letter to 23andMe?

  • 42% Yes. Regulators need to ensure that tests and their interpretation are valid.
  • 15% Yes. Such tests influence people’s healthcare decisions.
  • 10% Maybe. It’s unclear as to what the issue is.
  • 17% No. People have a right to their genetic data.
  • 13% No. No one will make a serious medical decision without getting a second opinion.

Stay tuned.

What about concordance of DTC genetic testing? What of it?

When mulling over my “Navigenics-and-Me” risk results in light of the 23andMe controversy, I wondered—as an experimental scientist—whether the same risk results would be obtained in an independent analysis of my saliva by 23andMe. Checking the literature for any DTC genetic testing concordance of evidence, I found a spot-on and revealing publication by Imai et al. in Clinical Chemistry entitled Concordance Study of 3 Direct-to-Consumer Genetic-Testing Services. Briefly, here are important snippets of what was reported.

BACKGROUND: Massive-scale testing of thousands of SNPs is not [in practice] error free, and such errors could translate into misclassification of risk and produce a false sense of security or unnecessary anxiety in an individual. We evaluated 3 DTC services and a genomics service that are based on DNA microarray or solution genotyping with hydrolysis probes (TaqMan® analysis) and compared the test results obtained for the same individual. 

METHODS: We evaluated the results from 3 DTC services (23andMe, deCODEme, Navigenics) and a genomics-analysis service (Expression Analysis). 

RESULTS: The concordance rates between the services for SNP data were >99.6%; however, there were some marked differences in the relative disease risks assigned by the DTC services (e.g., for rheumatoid arthritis, the range of relative risk was 0.9–1.85). A possible reason for this difference is that different SNPs were used to calculate risk for the same disease. The reference population also had an influence on the relative disease risk. 

CONCLUSIONS: Our study revealed excellent concordance between the results of SNP analyses obtained from different companies with different platforms, but we noted a disparity in the data for risk, owing to both differences in the SNPs used in the calculation and the reference population used. The larger issues of the utility of the information and the need for risk data that match the user’s ethnicity remain, however.

Although I’m not an expert in SNP-based genetic analysis, it seems that the aforementioned issues are addressable by industry-wide agreement to use the same SNP markers and associated medical databases (i.e., harmonization), and account for ethnicity—akin to what’s been recently reported for SNP-based human identity testing of different ethnic populations world-wide.

Further reading, if you’re interested (and I hope you are)

Frankly, I was amazed by how much has been published, said, or debated on the subject of DTC genetic testing that I’ve only touched on here, based on my personal experience to date. So, in closing, I decided to share a few links to items that I found to be especially thought provoking.

A November 2013 study abstract entitled No easy explanation for divergent attitudes regarding the medical utility of consumer genetic testing: Findings from the pgen study. This study was funded by NIH and announced in 2012 as having “[t]he goal to produce results that can be translated into recommendations to guide policy and practice in this rapidly emerging area.” Participants include more than one thousand customers of 23andMe and Pathway Genomics.

A scholarly (but not-so-easy-to-read) online paper entitled Myths, Misconceptions and Myopia: Searching for Clarity in the Debate about the Regulation of Consumer Genetics by Stuart Hogarth of Global Biopolitics Research Group, King’s College London, London, UK, funded by the Wellcome Trust. It concludes by stating that “[t]he choices we make as citizens about the technologies we use can have profound implications for the nature of our society. Shaping the future of genetic testing may be something which is better done as a collective policy rather than as individual consumers.”

Perspectives published in 2011 in Nature Reviews Genetics offered by five highly regarded experts—each in different fields—entitled The future of direct-to-consumer clinical genetic tests. The two questions posed to them for comment are:

  • What would be the fairest and safest way to regulate DTC genetic tests?
  • What should be the role of health professionals?

A blog entitled 23andMe DNA Test Review: It’s Right for Me but Is It Right for You?  provides a basic primer on DTC genetic analysis, and a string of ~70 comments that evolve over several years giving a flavor, so to speak, about differences in opinion.

As always, your comments are welcomed.