Picture this: The year is 2049. You’re sitting in your swanky San Diego high rise, watching the sunset as you sip on your kombucha (which has now replaced wine in terms of popularity) and listening to some slow jazz. All of a sudden your watch buzzes, notifying you that a package has arrived. You open the door and pick up the sleek white box, placing it on the table, and pressing your thumb on the button in the center. The package opens and inside lie three tubes, each with its own individual label. They’re your monthly medicine supplies—one for diabetes, one for cancer, and one labeled TEST KIT. Interestingly enough, you don’t have cancer, but to minimize your risk, your doctor has given you a custom “epi drug,” as these days all prescription medication is customized to each individual’s genome.
This scenario seems like something straight out of the future, but this reality is a lot closer than you and I might think. Thanks to epigenetics and its role in personalized medicine, designer healthcare might not be a long way off. I know what you’re thinking: Hold on… isn’t medicine already personalised? Touche, but only to a certain extent. Currently, allopathic medicine is mainstream, and it focuses on treating a disease’s symptoms. However, the precision medicine approach takes current treatment styles to a much more sophisticated level. Let’s go to the PMIF— the Precision Medicine Institute of the Future—or in other words a completely made up (but entirely plausible) institution to help me illustrate my point.
You enter PMIF, a large modern building, sign in using Face ID, and unfettered by the burden of human communication, you sit down and thumb through a magazine on the history of Precision Medicine. In his 2016 State of the Union Address, President Obama announced his budget, which would include $215 million dollars towards the Precision Medicine Initiative that would increase research on personalised medicine, with a special emphasis on improving cancer treatment (1). The approach was somewhat revolutionary, synthesizing information about a patient’s environment, epigenome, and lifestyle in order to treat, diagnose, and predict disease. Before you can finish reading the rest of the magazine, your phone buzzes with a notification “The doctor will see you now,” and you make your way to your digitally assigned room, passing underneath a large sign which reads “Everyone is truly Unique— PMIF.” While this appears a little cliche to you, it is scientifically accurate.
According to the “central dogma,” DNA contains genes, which are translated into RNA, which then creates the proteins that our bodies need. Seventh grade biology, right? Wrong. Like most things in life, this is more complicated than it initially appears to be and we can understand these complexities through the field of epigenetics. You see, genes are quite moody and express themselves in many different ways. If a methyl group is added to the DNA, or acetyl group to the histones, expression can change without changing the gene code at all, and the expression of one gene can be entirely different. These changes are typically adaptive, occuring in response to environmental cues and giving us layers of unique regulatory and environmental information around our genes. That’s why no two twins are truly identical, and why that sign was, in fact, scientifically “classy” (2).
After you’ve debated the validity of the sign for a few minutes, Dr. Renfre enters. “Hello!” he smiles as he pulls up your chart, “So last year we discussed… jumonji, correct?” he asks. No, Dr. Renfre was not playing a board game with you; the gene called jumonji (Japanese for cruciform) changes how it expresses itself over time, working with hormone regulators to promote cancerous cell growth and create treatment resistant cancers (1). Last year, Dr. Renfre identified this gene after a test and explained that jumonji had not changed to a cancer-promoting cell yet, but it had the potential to do so. However, he managed to assuage your fears with another truthful one liner “Our genes do not dictate our fate.” Epigenetics means our genes are constantly changing, and scientists are working on developing certain drugs so that we can change them for the better. Here’s an example: In 2013 Angelina Jolie found she had BRCA-1—a gene which malfunctions to lead to breast cancer, and underwent surgery to reduce her risk (leading thousands of other women to do the same in what is referred to as the Jolie effect). Now, scientists are mapping out the different methylation patterns of genes in order to develop drugs that can combat the negative instances. As for you, well that’s where the newly developed medication came in.
“Ok,” Dr Renfre resumes, “So I know all about your diabetes diagnosis. I can see your glucose readings, and you know diet and lifestyle are important to a point, and. You’ve made tremendous changes, but we can help you even more.” You nod eagerly. Last time you did this, Dr. Renfre was able to cut your cancer risk in half at the very least, so why wouldn’t you agree?
He explains his proposal, “You know, for the longest time drugs have operated under a one-size fits all approach. If you’re above a certain age you’ll get metformin for your diabetes. If it doesn’t work well I’ll give you Glycet or Cycloset you know?”
You don’t know, but you nod your head anyways. “But,” he continues, “Epigenetics, what we do here at PMIF, transforms this paradigm entirely and provides a better indicator for clinicians like myself as to how a patient is metabolizing and progressing with certain medications. The epigenome is always changing; it has great potential as a biomarker, an internal clock we can use in treatment to track how the body is handling a particular disease. That’s what we want to do with you.” Dr. Renfre proceeds to detail the workings of a new medication, a customized diabetes medication based on your unique polymorphisms that make the traditional prescription of metformin obsolete (3). Before he leaves you to consider, he hands you a pamphlet from Soustava, a systems biology company that manufactures the custom drugs. The whole prospect seems appealing—the Soustava pamphlet touts a “renowned understanding as to how genes are regulated and how we can use drugs to break harmful regulation cycles, restoring the balance between our genes and the environment.” Who wouldn’t want that?
Well, PMIF is not always all it’s cracked up to be. A recent study revealed that a majority of research in epigenetics and personalised medicine is centered around European populations, meaning that researchers may miss the opportunity to understand more about the genetic links with diseases like heart disease and diabetes that are prevalent in minority populations. For instance, the PAGE study at UNC-Chapel Hill found that certain gene variants were associated with not only a higher disease risk, but also a greater likelihood of disease mismanagement (3). This is only the tip of the iceberg when it comes to the research, but we must be hypervigilant. If precision medicine takes a holistic approach to treatment, its research must also take a holistic approach by serving diverse populations and communities.
Back in your apartment, you down your medicine with kombucha (don’t try this at home) and eat one of PMIF’s custom health meals. As you eat, you make a mental toast to precision medicine, to PMIF, and to Dr. Renfre, for allowing you to enjoy this fine evening disease free.
(1) Flipp, Fabian. “Can Epigenetics Help Fuel Personalized Medicine Revolution in Cancer Treatment?” Genetic Literacy Project, 6 Jan. 2019, geneticliteracyproject.org/2017/04/27/can-epigenetics-help-fuel-personalized-medicine-revolution-cancer-treatment/.
(2) Kronfol, Mohamad M, et al. “The Role of Epigenomics in Personalized Medicine.” Expert Review of Precision Medicine and Drug Development, U.S. National Library of Medicine, 2017, www.ncbi.nlm.nih.gov/pmc/articles/PMC5737812/.
(3) Chapel-Hill, UNC. “Lack of Diversity in Genomic Research Hinders Precision Medicine for Nonwhite Americans.” ScienceDaily, ScienceDaily, 19 June 2019, www.sciencedaily.com/releases/2019/06/190619142605.htm.