Point-of-Care PCR 2.0

  • Ubiquitome Quickens Pace of POC Apps for Its Freedom4
  • Cepheid Unveils its POC Diagnostics System
  • Hopkins Crew Brews “Coffee Mug-Sized” Gizmo for Fully Automated Chlamydia Testing
Kiwi Dr. Jo-Ann Stanton holding Ubiquitome’s Freedom4 at Tri-Con 2015

Kiwi Dr. Jo-Ann Stanton holding Ubiquitome’s Freedom4 at Tri-Con 2015

Regular readers of this blog will recall a recent byline exclaiming “Honey I Shrunk the qPCR Machine”, which spotlighted the unveiling of startup company Ubiquitome’s first point-of-care (POC) product—Freedom4—developed in New Zealand. Up until then, this far away—for me—exotic island country brought to mind folks fondly nicknamed Kiwi—after the native flightless bird, not Chinese fruit. Mightily impressed by this tiny but powerful qPCR device, I vowed to thereafter keep an eye on these Kiwis’ democratized POC apps enabled by its nifty handheld 4-sample high-performance qPCR device.

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Top Picks from Tri-Con 2015

  • “Honey I Shrunk the qPCR Machine” Tops Presentations
  • High School Student Wins Popular Vote for Best Poster
  • BioFire Defense FilmArray is More Interesting Exhibitor
  • Extra Bonus: Swimming with the Sharks

The 22nd International Molecular Medicine Tri-Conference—better known as Tri-Con—took place on Feb 15-20 in San Francisco, where I and 3,000+ other attendees from over 40 countries took part in a jam-packed agenda. In this blog I’ll briefly share my top 3 picks—and an “extra bonus”—but first some insights into the challenges involved in navigating a large conference like this.

The first challenge was scoping out four simultaneously occurring “channels”—diagnostics, clinical, informatics, and cancer—to select as many interesting items as possible from all the presentations (500), panel discussions (30), posters (150), and free “lunch-nars.” The new Tri-Con’15 app with a word and name-searchable agenda (including abstracts) made this easier than previous years. I was even able to put selected items into a calendar/to-do list with 15-min reminder alarms—very slick and convenient. Every big conference should have an app like this!

The second challenge came once I was physically onsite. It took a bit of effort to navigate from one room to another in the huge, multi-room Moscone Center without GPS guidance. I was also struggling to make it to the talks and events on time without getting hijacked by bumping into friends—which happened a lot.

The third and final challenge had to do with posters. Given all of the other exciting options during the conference, I really had to focus to stay on-task and make sure I was present at my poster at the specified times, yet alone try to get around to the other posters of interest. This was definitely not easy, since my poster entitled Pushing the Limits of PCR, qPCR and RT-PCR Using CleanAmp™ Hot Start dNTPs attracted a steady stream of interested visitors. But that’s a great challenge to have, so I can’t complain too much.

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mtDNA Replacement: Eliminating Disease or Creating Designer Babies?

  • Mitochondrial DNA Replacement to Preclude Mitochondrial Disease Shown Feasible in Monkeys
  • US FDA Advisors Ponder Pros and Cons for Allowing Human Clinical Trials Amidst “Designer Baby” Concerns
  • UK Government Decision “Up in the Air”


Before jumping into the headline and bylines of this post, I thought it would be worth sharing TriLink’s connection with mitochondrial DNA (mtDNA), as well as provide a bit of background about mtDNA and diseases related to it.

TriLink recently introduced its mitochondrial DNA (mtDNA) PCR-sequencing primers (mitoPrimers™) and mtDNA master mix for forensic science and casework. These products have been used by several well-known experts in mtDNA forensics, including Prof. Rhonda Roby, a well-known expert in mtDNA forensics. Prof. Roby’s expertise in mtDNA sequencing extends beyond forensic applications to academic interests in disease-related mtDNA dysfunction, as described in her recent publication in Nature Scientific Reports.

To better understand those interests, I researched mtDNA diseases at an NIH.gov website and found that, while mtDNA is only a “tiny” (~16,569 base-pairs) genetic component compared to genomic DNA (~2 billion base-pair), and encodes only 37 genes compared to ~20,000 genes for genomic DNA, the list of mtDNA related diseases is lengthy.

The vast majority (90%) of the energy needs of the human body are provided by mitochondrial oxidative phosphorylation that takes place entirely in mitochondria, and is a highly efficient system for producing the energy required to maintain the structure and function of the body. Consequently, according to the NIH.gov website, mutated mtDNA disrupts the mitochondria’s ability to efficiently generate energy for the cell, leading to organ-related health conditions. These conditions can be serious and are most pronounced in organs and tissues with high energy requirements, such as the heart, brain, and muscles. Frequently observed symptoms include muscle weakness and wasting, problems with movement, diabetes, kidney failure, heart disease, loss of intellectual functions (dementia), hearing loss, and abnormalities involving the eyes and vision.


Taken from “Powerhouse Rules: The Role of Mitochondria in Human Diseases,” online coursework at MIT (ocw.mit.edu) via Bing Images.

The image (right) depicts multiple copies of circular mtDNA that reside in mitochondrial organelles external to a cell’s nucleus (in blue), which contains genomic DNA. Whether or not these organelles evolved by free-living bacteria that were taken inside a human cell-to-be (aka endosymbiotic theory) is an evolving—pun intended—debate worth reading about if you’re intrigued—as I am—by pondering how our cells came to be what they are.

Interestingly, women’s egg cells have many copies of mtDNA while men’s sperm cells have just enough to enable it to swim to the egg and fertilize it. The mtDNA of the sperm usually disappears once fertilization occurs. On the other hand, the mtDNA of the egg pass on to all of a woman’s children (male and female), but only women pass on their mtDNA from generation to generation. This maternal aspect of genetics is depicted in the cartoon below, posted by genetic-ancestry company 23andMe to celebrate Mother’s Day.

Taken from blog.23andme.com via Bing Images.

Taken from blog.23andme.com via Bing Images.

Unfortunately, we might not always be thanking Grandma for her mtDNA. In her daily blog, Mighty Mito Mom, Amy Boyd chronicles the challenges and experiences as a Mom whose daughter—affectionately called Little Miss Mollypop—has a mitrochondrial disease. I also found numerous YouTube videos that give a real sense of how families struggle with mitochondrial disease, such as this poignant example involving three generations affected by mitochondrial-related conditions. These examples raise the question, can something be done to preclude mtDNA disease by substituting “good mtDNA” for “bad mtDNA” during in vitro fertilization (IVF)?

The answer is yes, but the process involves what some view as three parents—two females and one male. As you may imagine, the procedure prompts considerable concern and controversy.

Mitalipov’s Mitochrondrial Manipulations

I’ve “borrowed” this catchy alliterative heading from the title of a March 2014 NY Times story. The article is by Sabrina Tavernise about Oregon Health and Science University Dr. Shoukhrat Mitalipov, who has developed a procedure to help women conceive children without passing on their mtDNA genetic defects. Salient snippets of this article are as follows, including this self-charactrization by Mitalipov: “my colleagues, they say I’m a ‘mitochondriac,’ that I only see this one thing. Maybe they are right.”

Dr. Mitalipov, 52, has shaken the field of genetics by perfecting a version of the world’s tiniest surgery: removing the nucleus from a human egg and placing it into another. In doing so, this Soviet-born scientist has drawn the ire of bioethicists and the scrutiny of federal regulators. Credit Leah Nash, NY Times.

Dr. Mitalipov, 52, has shaken the field of genetics by perfecting a version of the world’s tiniest surgery: removing the nucleus from a human egg and placing it into another. In doing so, this Soviet-born scientist has drawn the ire of bioethicists and the scrutiny of federal regulators. Credit Leah Nash, NY Times.

About one in 4,000 babies in the US is born with an inherited mitochondrial disease. These diseases are terminal, there is no known treatment, and few of these afflicted children live into adulthood. Women who carry mtDNA mutations are understandably eager not to pass them to their children. Remember, although sperm carry mitochondria, they are usually degraded shortly after fertilization, so mitochondrial diseases are passed down through the mother. Dr. Mitalipov’s procedure (shown below) would allow these women to bear children by placing the nucleus from the mother’s egg into a donor egg whose nucleus has been removed. The defective mitochondria, which float outside the nucleus in the egg’s cytoplasm, are left behind, thus eliminating the possibility of passing along defective mitochondria.

Those of you interested in Mitalipov’s published feasibility results with human oocytes can read a 2013 report in Nature, and a 2014 review of promises and challenges in Fertility and Sterility entitled “Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases.”

Mitochondrial DNA replacement could help carriers of severe disease have healthy children. Credit K. Sutliff, Science.

Mitochondrial DNA replacement could help carriers of severe disease have healthy children. Credit K. Sutliff, Science.

Are “Designer Babies” on the Horizon?

While some advocates of this procedure say it’s a “major breakthrough,”others aren’t as enthusiastic since the resulting baby would carry genetic material from three parents—the mother, the host egg’s donor and the father—an outcome that ethicists have deplored.

That specter drew critics from all over the country to a hotel in suburban Maryland in February 2014. It was here that Dr. Mitalipov tried to persuade a panel of experts convened by the FDA that the procedure, which he has pioneered in monkeys, was ready to test in people.

Some experts voiced concerns about unintended consequences, such as introducing new genetic mutations into the human gene pool. Others warned that it could be used later for something ethically murkier—perhaps, said Marcy Darnovsky, executive director of the Center for Genetics and Society, “to engineer children with specific character traits.”

Darnovsky’s assertion of a slippery slope situation possibly leading to “designer babies” is not new, and can be read about in a lengthy Science perspective entitled Stirring the Simmering “Designer Baby” Pot written by Thomas H. Murray. The metaphorical “pot” that he refers to ties Mitalipov’s proposed procedure to a 2013 patent granted to 23andMe—a controversial want-to-be genetic testing company currently foiled by the FDA. This “hot button” patent covers genetic calculations that enable would-be parents “to select a donor and view other possible phenotype of the hypothetical child resulting from the recipient’s and the donor’s gametes.”

Dr. Mitalipov waved off those warnings, according to Tavernise, by noting that mtDNA comprises just 37 genes, which direct the production of enzymes and molecules that the cell needs for energy. Those genes, he says, have nothing to do with traits like eye and hair color, which are encoded in the nucleus. She quotes Mitalipov as saying that “there are always people trying to stir things up. Many of them made their careers by criticizing me.”

“Suspended Animation”

In his Science perspective, Murray observes that “it is unrealistic to expect the US policy lacuna [gap or missing piece] over assisted reproductive technologies to be filled any time soon. Regulation of preimplantation genetic diagnosis remains in a ‘state of suspended animation’—according to a cited publication.

He adds that “professional self-regulation likely works well when the interested professions reflect a well-established public consensus. But when it comes to empowering parents to decide what sort of children they have beyond questions of serious childhood diseases, professional organizations cannot even agree on the appropriate ethical framework.”

Murray concludes by stating that “discussion of the ethics of mitochondrial manipulation cannot be postponed indefinitely. With little prospect of sensible legislation in the near term, and conflicting guidance from professional organizations, a national conversation about current and emerging technologies shaping the choices that parents will have is urgent. The UK conducted a similar exercise a decade ago that combined polling, focus groups, and the Internet.”

Status of mtDNA Replacement in the UK

In Britain, the government has issued draft regulations that would govern clinical trials of mtDNA replacement in people. If accepted into law by Parliament, such trials (which are now banned), would be allowed to go forward, although regulators would have to license any clinical application.

Polly Toynbee of The Guardian reported in February 2014 that, while a year has passed since the public was consulted at extraordinary length on the ethics of mtDNA replacement to prevent the birth of children with incurable genetic diseases—with most of the public saying yes, go ahead—the government has “dragged its feet.”

Inquiring about its progress with the Department of Health a couple of weeks before drafting her report, the answer was, “it’s up in the air.” Pressed on the question the day before publishing, she was told that draft regulations may appear next month. But the public will have to be consulted again, for a further three-month period. Polly opined that, since this procedure “arouses deep passions, plentiful responses are expected” and it will take yet more months to consider them. Doubts remain about the government’s eagerness to push this through parliament, rousing a controversy close to the general election, she added.

My comment is that difficult policy decisions and political party concerns for reelection seem to be similar on “both sides of the pond,” as the UK and the US are referred to.

Newcastle University neurologist Prof. Doug Turnbull, who is co-leading investigations with embryologist Dr. Mary Herbert, has been putting pressure on the government to prepare legislation that will allow experts in Newcastle to use human embryos containing DNA from three people to be used in clinical treatment, according to an earlier report.

Ms. Toynbee points out that the Human Fertilization and Embryology Authority (HFEA) conducted its scientific review of the procedure’s safety and efficacy and concluded back in 2011 that it would be unethical for the government not to press ahead, to prevent any more needless suffering. Toynbee was a member of the HFEA’s oversight group that supervised a massive public consultation, ensuring these complex issues were fairly aired and comprehensible to all.

Overall, the public was in favor, she says, and adds that when randomly selected people looked at the evidence they didn’t think this was a slippery slope that would lead to “designer babies,” or that it amounted to “three-parent IVF,” as there is no genetic effect on identity. The HFEA recommends that mitochondria are treated like tissue, a kidney for example—so donors would not be considered ‘parents.’

She adds “parliament is often less rational than the public. Stuffed with the religious and rabble-rousers who stir up fears of Frankenstein babies, many in both houses will make noisy speeches, ignoring the science.” That despite an estimated 73 people dying each year from mitochondrial disease, many of them children. The impact is even greater when you consider that some mitochondrial diseases go undiagnosed and that over 2,500 women of child-bearing age carry faulty genes – putting their children at risk.

Ms. Toynbee concluded her story by saying that “just as I reach the end of writing this, a call comes from the Health Department: it wants me to know that it is still absolutely committed, and regulations will be out soon. Why the year’s delay? Ah, um. When will the regulations go to parliament? ‘By the end of the year’ was the reply. Left so close to the election, let’s hope No. 10 strategists don’t veto it.”

As always, your comments are welcomed.


After writing this blog, The New York Times Magazine featured a lengthy cover story by Kim Tingley entitled One Child, Three Parents. Also, a lengthy and freely available article by Ewen Callaway was published in venerable Nature magazine. Overall, the same pro and con issues are presented by Callaway, along with simplified diagrams showing methodological differences between pronuclear transfer and maternal spindle transfer techniques for genome transfer to prevent children from inheriting their mother’s mutant mitochondria. I found this article’s lead-in graphic (credited to Vasava) show below to be symbolically riveting and worth sharing here.


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 B. Agus, M.D.


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.


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.


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.