The Darker Side of Genetic Testing
Lessons from ‘DNA is Not Destiny’ by Steven J. Heine
I remember a time where advertisements and sponsorships from the genetic testing company 23andMe would flood YouTube. Some individuals from channels which I subscribe to would first get their DNA sequenced by 23andMe and other direct-to-consumer genomic companies, and share snippets of the findings online for all to see. These companies provide two categories of information, the first being their geographic ancestry, or which part of the world their ancestors came from, and the second is their genetic health risks, which states what diseases they are more prone to because of their genetic disposition.
At that time, as I was quite a bit younger and not yet enlightened about genetics, I was pleasantly amazed at the potential of genetic testing. At a relatively low cost, you could unlock your past, present and future. You could reveal your heritage, better understanding your roots and your ancestors. You could use the information to make better-informed decisions in the future regarding your own health, getting more checks done and being more attentive in some of the more vulnerable aspects, while saving money on the lower-risk aspects. It’s a one-time investment of money (even though it is not cheap), where the returns in terms of information will last forever and beyond. Who would not want to be tested?
And yet, being one of the topics covered in the book DNA Is Not Destiny: The Remarkable, Completely Misunderstood Relationship Between You and Your Genes by Steven J. Heine, genetic testing in reality is fraught with inaccuracy, also leading to a potential misinterpretation of your genes. These problems are further exemplified by us humans’ natural tendencies to perceive genes from an essentialist perspective, a characteristic which is exploited by many direct-to-consumer genomics companies in order to increase demand.
Hence, this article draws important lessons and concepts from Heine’s book, and aims to enlighten the public about what genes truly are, how to perceive them, and the problems with genetic testing.
A Genetic Misunderstanding
“What are genes?”
If you ask this question to a person with a superficial understanding of genetics, or even to people with a more in-depth understanding who would give a simplified answer, they might give this answer:
“Your genes is analogous to a blueprint of you. It contains information to make, well, you.”
This ‘blueprint’ or ‘recipe’ analogy is commonly used to describe genes to a layperson, because it draws parallels between something which people are unfamiliar with and something which most are familiar with. However, this analogy is not entirely accurate, because as compared to the simpler mechanical systems which blueprints and recipes instruct you to build, building you out of genes is a lot more complicated.
In reality, your genes are just sequences of DNA in your genome which code for proteins, which are important for a vast array of functions in your cells and outward to your whole body. The process is described as the central dogma, where DNA in the nucleus of your cells are first transcribed into messenger RNA, or mRNA. The mRNA then leaves the nucleus and goes to the ribosomes, which reads the information on the mRNA and translates it into the correct amino acid chain, subsequently folding to form proteins. Those proteins each have numerous cellular functions to control.
Mind you, this is an extremely simplified explanation of the process of making proteins from DNA. In actual fact, there are many regulatory processes in between the steps which contributes to the final product. However, a good proportion of people are unaware of this, and even worse still, are not satisfied with the answer “it’s complicated”. Our brains want answers, and if not presented with a satisfying one, will make logical short cuts and assumptions to get an answer that sounds ‘reasonable’ and follows ‘common sense’. In this case, laypeople usually think of genes as the genes from Mendel’s peas, where one particular allele codes for green peas, while another codes for yellow peas. Gene A codes for phenotype A, whereas gene B codes for phenotype B, and there are only straightforward, causal relationships between genes and the organisms’ appearances. However, this is not always the case. In fact, this is not even the case most of the times. Mendel was actually extremely lucky at the time to find and breed a species where there were straightforward genotype-phenotype relationships. When he tried to repeat his experiments for other organisms, he could not replicate his initial successes.
In DNA Is Not Destiny, Heine describes that people have a natural tendency to perceive genes as an essence, which is something unique and immutable tagged to every individual. He terms this as ‘essentialist thinking’, which potentially leads to a lot of problems in society, one of them being the misunderstanding in genetic testing.
Genetic Testing and Ancestry
One of the reasons to get genetic testing is out of curiosity about your ancestors, basically, where you came from. Most of us would know where our parents were born, and some would have information about their grandparents, but beyond that, it gets blurry for the next few generations. To satiate that craving for information of where your great great… great grandparents might have been born, people might get themselves genotyped and find out about their ancestry.
Direct-to-consumer companies such as 23andMe could utilise three aspects of our DNA which reveals ancestry. The first and second are mitochondrial DNA, which comes exclusively from your mother, tracking maternal ancestry, and the Y chromosome, which comes exclusively from your father. Any mutations appearing on these two types of DNA would remain for generations to come, becoming a new feature which only your generation and generations after have. Since people could migrate around the world, even hundreds of generations back, this feature would pop up around the world, and one could trace it back to the ancestors.
The third and last feature is genetic drift, which describes a process when random factors influence which alleles will become more common in subsequent generations. This results in certain alleles becoming more common in certain parts of the world as compared to others. By looking at a snapshot of thousands of alleles across the entire genome, it is possible to estimate a person’s geographic ancestry.
Despite having three distinct methods to discern geographic ancestry, genetic testing is still terribly unreliable and inconsistent, a serious limitation which most direct-to-consumer companies do not tell you. Heine draws the example of Oprah Winfrey, who wanted to do philanthropic work at her ancestral roots in Africa. She initially got her DNA tested and found that she was a Zulu, but got tested again as part of a TV series, African American Lives, and found that she had three exact matches, but no Zulu matches.
This inaccuracy in ancestry prediction comes from a few possible sources. Firstly, references databases to draw inferences of ancestry are taken from contemporary groups, which might differ from ancestral groups. The existing database might not be extensive, as there are many populations around the world that have not yet been sampled. Moreover, the analysis techniques that each genomics companies use is not transparent to customers, and there are few legislations and standards implemented to enforce scientific accuracy. Lastly, of course, even employing good techniques and a representative database, ancestry tests are still mostly predictions based on data, which is inevitably imprecise.
The bigger problem comes when direct-to-consumer companies such as 23andMe do not highlight these limitations to consumers, and frame their results in such a way that it instills overconfidence in the accuracy of their results. If you take this test out of curiosity, then you would likely not be affected by the results, accurate or not, but if you, like many, place heavy emphasis on the results, looking to find a sense of identity in your genes, then inaccurate results could get you terribly disheartened.
Genetic Testing and Health
Another reason to approach direct-to-consumer companies for genetic testing would be to find out your risks of developing certain diseases, which are influenced by your genetic disposition. A rather famous example stems from actress Angelina Jolie, who chose to undergo a double mastectomy, a surgical procedure to remove both her breasts, upon receiving genetic testing results that she carried a dangerous mutation in the BRCA1 gene. That, alongside her family’s history of contracting breast cancer, led to the estimation of her having a 87 percent chance of developing breast cancer during her lifetime.
This example would be pleasant news for the majority of us consumers, because it highlights the potential benefits of genetic testing on our health and healthcare services. However, as you will find out, the ugly truth of the matter is that genetic testing is no where as reliable as the majority of us think it is, and holding a flawed perspective on the accuracy of genetic testing could lead to more harm than good.
Firstly, because of our natural tendencies to default to essentialist thinking, we wrongly assume that genes are the ultimate causes of diseases. We think of the results of genetic testing as something akin to a diagnosis of the disease, or on the flipside, the lack of it. This shifts the way we approach our own health, as well as medicine and healthcare. Even if you feel perfectly fine and well, getting genetically tested is, as Heine describes it, visiting an oracle. In Angelina Jolie’s case, it looks past all outward signs of a young and healthy woman, conjuring the diseased essence that lay below, a disease which seems to be inevitable because of her genome.
If you received results from genetic testing which shows that you have a greater risk of contracting disease A, while having a lowered risk of disease B, your strategies and habits would surely change to an extent, now with this newfound information. Maybe you would get yourself tested more often for prostate cancer, or shift your diet towards one with more fiber. These are undoubtably healthy habits, but on the flipside, if the test results show a decreased genetic risk factor for Type 2 diabetes, some would be less mindful about their caloric intake, and get tested less for the disease.
The point is that people are treating mere predictions as inevitability and diagnoses. To make matters worse, these predictions may not even be accurate. To reinforce a fact from the previous section of this article, there is a lack of legislation which enforces a certain standard of scientific legitimacy, even for medically-related information. Direct-to-consumer companies might even want to give definitive predictions, even if the results are largely insignificant, in order to make consumers believe that their service is of value to them. Just like the Oprah Winfrey case above, Heine also got his genetic risk factors analysed by three different direct-to-consumer genomic companies, and got drastically different results for each. He notes that 23andMe tends to exaggerate their findings to give more definitive results.
Our genes undeniably have a role to play in our susceptibility to contracting diseases, but our ability to make accurate predictions is limited by two factors. Firstly, most genes have an extremely weak correlation with the onset of diseases, to the point of insignificance. Hence, finding significant predictive power even with a set of many genes of a certain disease is very difficult. Secondly and more importantly, our scientific understanding of the genes is far from complete. All we have is the statistical correlation between gene and disease. We do not fully understand how a gene can influence another and how the combination of the genes lead to an increased/decreased risk of the disease. We do not have representative data to draw conclusions for every population. We also do not know every gene which is connected to the disease. For all you know, there is another set of genes which are not tested by these direct-to-consumer companies, but influence the onset of those diseases.
Conclusions
I am a staunch supporter of the scientific method, and I do believe that our genes can tell us a lot about our biology. However, it is important to believe in good science which is backed up with sound research, as well as understand the potential and the limitations of our present scientific capabilities.
As of now, our understanding of the predictive power of genes is insufficient to derive methods effective in guiding the general population towards better-informed health strategies and decisions. There are exceptions, of course, such as that of Huntington’s disease, where the number of CAG repeats along the HTT gene on chromosome 4 acts as a genetic switch, in which suffering from Huntington’s disease is entirely dependent on that gene. The vast majority of genes, however, have at most a weak correlation with the onset of diseases. Our genes can also give estimates on the geographic location of our ancestors, although it is not as accurate as it seems a lot of the time.
Personally, I find it disturbing that many direct-to-consumer companies are exploiting the fact that the majority of the population is unfamiliar with genetics, letting them see what they want to without including the necessary disclaimers to highlight the blurry nature of the results. They capitalise on the good name of science to their profit, tainting it in the process.
Until this field of research becomes more reliable, why not appreciate who we are now instead of obsessing over how we were born? Other than our genes, our environment and lifestyle habits built over the years shape who we are today, and what we do now affects the future.
“You gotta let go of that stuff from the past, ’cause it just doesn’t matter. The only thing that matters is what you choose to be now.”
-Po from Kung Fu Panda 2
