by Ronnie S. Stangler, M.D.
Just days before Christmas, 2019, the Pentagon issued a warning to military personnel not to engage in mail-in DNA tests (often known as direct-to-consumer genetic tests or DTC, such as 23andMe, ancestry.com, etc.), exhorting that they create security risks, are unreliable and could negatively affect service members’ careers. Stark. Given the state of world turmoil on that day, it is impossible to believe that the Pentagon would make such a radical communication unless a sensitive breach (or breaches) had already occurred.
The Pentagon was articulating what privacy experts in medicine and genetics have been actively admonishing for some time. DTC genetic testing is not simply harmless infotainment to be distributed in holiday stockings or passed out during Chanukah festivities.
Let’s dissect this matter more thoroughly, as c. 30 million consumers have already partaken of such tests. What does that mean for them (and for you) and what does that portend for the advancement of the science?
A Little Background
Genes are a universal inheritance and legacy – they have been so since the onset of humankind. Historically they have been an invisible presence. But we have now entered the era of the genome, the era of transformative extraordinary biotechnology. Now the invisible, our genes – an essential building block of humanity – can not only be fully seen, but they can also be read like a book, and, like the words in a book, they can be altered, edited and enhanced.
The specter of profound change in health and medicine looms large: an exciting moment in time when science fiction has blurred into science fact. But this moment is also rife with over-promise, hype and potential to harm. As we engage in the serious science of how our genes can enhance our health, wellbeing and longevity, we must ground such conversations with a clear understanding of what is possible today and what remains to be fully realized. And to understand, if we engage in genetic analyses, what exactly have we signed up for.
Genes: building blocks of life
Each of our cells contain a set of genes which provide comprehensive instructions constituting the masterplan for our lives. In conjunction with our environment and lifestyle, our genes determine fundamentals of who we are: our appearance; idiosyncratic traits; how we survive and prosper; how we become ill; how we age.
While genes do not constitute absolute destiny, they are a critical ingredient to fully understanding and optimizing our lives. Extraordinary escalating advances in science have facilitated not only our understanding, but increasingly our agency. We can now alter genes through radical gene-editing technologies such as CRISPR.
Genetics vs Genomics
Genetics is the study of heredity and individual genes. Many of us first learned about genetics in high-school biology as we contemplated Mendel’s pea plant experiments of the 1860s.
Genomics, however, is the study of an organism’s complete set of genes, called the genome, the entirety of its DNA. The importance of studying all of our genes through genomics is that most traits (such as height, intellectual prowess, athletic ability), most common medical disorders (such as heart disease, diabetes, obesity) and most emotional and psychiatric conditions are a function of many genes acting together in concert with our lifestyle and environment.
The genome can be analyzed through a process called whole genome sequencing (WGS), that is the sequencing of all of our genes, unlike DTC testing which involves analyses of small portions of preselected genes.
The first human genome was sequenced in 2003. This fifteen-year project cost over $3B. Today, we can analyze the human genome for less than $500 within weeks.
Direct to consumer genetics testing: the price you really pay
30 million customers have already embraced DTC genetic testing. It has been estimated that by 2021, over 100 million people will have utilized such analyses.
Motivations for testing range from curiosity about personal health, concern about family vulnerability to medical disorders, questions about ancestry, and sometimes simply a desire for “infotainment” (everything from dating advice, athletic ability to wine preferences).
However, what customers receive in return from DTC products is often pseudoscience, misleading and incorrect. And they pay for this with potentially irreparable loss of privacy, and at times false and dangerous reassurance about lack of medical vulnerability.
Unlike WGS, DTC tests utilize a technology called genotyping. Genotyping compares small segments of a customer’s DNA (less than .01% of our total), to discrete variations of DNA known to be associated with specific traits or disease entities. But the company preselects and determines what is studied.
For example: 23andMe only tests for three genetic BRCA variants, although more than 1,000 BRCA variants are known to increase breast and ovarian cancer risk. 90% of participants who carry a BRCA mutation are missed by today’s 23andMe test.
By the end of 2020, 90% of Americans of European descent will be personally identifiable on the basis of DTC genetic testing of relatives. So even if you now reject such analysis for yourself, if your second or third cousin has been tested, your entire family is vulnerable to identification.
The DTC industry has made friends with law enforcement. In conjunction with genealogy sites such as GEDmatch, it is now possible to combine data from DTC with genealogy data to identify specific individuals. Solving the case of the Golden State Killer using such data was the first in a series of over 70 murders and rapes that have been resolved through consumer sites.
Many consumers might support catching serial killers in this surreptitious manner, but the bar can be lowered without their consent. Will future analyses be used to track down perpetrators of minor criminal infractions or proponents of political or religious groups? A slippery slope. Interestingly a pure forensics firm has recently purchased GEDmatch. How they use its data will be their decision, not the decision of all those who contributed their DNA and genealogy information for entirely different purposes.
Ultimately, as many business analysts have long suggested, these slickly packaged attractive little DTC kits which collect saliva and purport to provide information about wine preferences and dating, as well as health, may always have cloaked an alternative stealth business model, specifically the collecting of DNA to be sold to other corporate entities like forensics and pharmaceuticals companies for entirely different purposes. In 2018 GlaxoSmithKline purchased exclusive rights to use 23andMe data for drug development for $300 million. Your DNA is now entirely out of your hands and out of your control.
Regulation of the consumer genetics industry, especially within the United States, is dangerously lax. The only two pieces of federal legislation that afford some protection, HIPAA and GINA, are limited in scope and applicability. The loopholes are stunning. Based on genetic testing, you can still be denied access to life insurance, long-term care and disability insurance. You are not fully protected against employment discrimination nor guaranteed access to health insurance.
Genetics is not a solo sport. Any choice made by one individual has potential impact on every other member of the family. Past, present and future.
Whole genome sequencing as an alternative
Alternatively, WGS provides a literal master blueprint of the entirety of one’s genes. Some have compared the difference between genotyping and WGS to the difference between a tricycle and a race car.
While the genotyping technology underlying DTC involves a review of 600,000 “letters” of our genetic code, WGS reviews the totality of six billion pieces of that code. The WGS industry is strictly regulated, governed by law and operates with highest evidence-based technical medical standards and protection requirements for those they serve.
Once your full genome is sequenced, it becomes a resource for life. It can be reanalyzed on an ongoing basis to incorporate new insights and interpretations made available through medical research.
WGS will provide actionable insights about pharmacogenomics (how one responds to particular medications), disease risk, and understanding about what one may have passed on to one’s children.
Understanding our genomes is the foundation for personalized precision medicine and we can directly participate in that dramatic health care revolution.
But we should be making best personal decisions only with partners who merit our trust. We may decide to participate in medical research. But this must be our decision, with informed consent and understanding of consequences, rather than a decision made for us by an unknown corporate entity whose motive is their profit, not our individual health, well-being or privacy.
Genomics bodes an extraordinary future with elimination of malignant disease, enhanced health and well-being, and healthy longevity, but it is not without risks and challenges.
There is wonder in our genes. Let us get to know them with the respect they, and we, deserve.
Ronnie S. Stangler, M.D., physician and psychiatrist, is the Founder of Genome Advisory, based in New York City. Dr. Stangler consults with individuals and global families to utilize the DNA science of genomics to enhance their strategic plans regarding health, risk and legacy.
She is a Clinical Professor of the Department of Psychiatry and Behavioral Sciences at the University of Washington, and has served as an Advisor to the Department of Genetics, Harvard Medical School.