Beyond the Code: Rethinking the Role of Genetics in Clinical Medicine

Is the genome like a master key? The answer to disease, dysfunction, and individual variability. While genetics has undoubtedly unlocked powerful insights, its primacy as a therapeutic target is, in many ways, overstated.

Yes, genes are fundamental. They are code—an essential set of instructions that defines the blueprint of life. But within a species, genetic variation is surprisingly limited. The genes themselves differ relatively little from one person to the next. What truly matters is not the static sequence of DNA, but which genes are expressed, when, how much, and in what context.

That’s the realm of epigenetics—a dynamic, responsive layer of regulation that governs how the genome is read. Epigenetic factors turn genes on and off, modulate their expression, and ultimately shape the proteins that drive function and form. This regulation is profoundly influenced by the environment, lifestyle, diet, stress, circadian rhythms, and even social interactions.

But the complexity doesn’t stop there. Once a gene is transcribed and translated into a protein, there are still multiple levels of control: post-translational modifications, folding, trafficking, and cellular localization all determine whether that protein fulfills its intended purpose. Misfolded, misdirected, or dysregulated proteins can cause dysfunction regardless of whether the underlying gene was “normal.”

And that’s just the ‘human genome’ side of the equation.

We now know that our microbiome—the vast ecosystem of microbes living in and on our bodies—contributes significantly to our metabolism, immune function, neurological health, and even gene expression. These microbial genes outnumber our own and interact with our cells in complex, bidirectional ways. Yet the microbiome, too, is shaped not just by inheritance but by diet, medication, environment, and behaviour.

In short: genetics is the map, not the journey.

In clinical medicine, placing too much emphasis on genetic testing or treating the genome as destiny is both reductive and limiting. We risk missing the most modifiable, actionable layers of biology—those that sit above the genome, shaping and being shaped by the lived experience of the individual.

This is why phenotype-based or metabolome-based approaches—which focus on what’s actually happening in the body—will be far more useful in guiding treatment. Measuring metabolic outputs, inflammatory markers, mitochondrial function, hormonal states, and other real-time biological signals gives us a direct window into health and dysfunction.

If we’re truly interested in personalization, prevention, and optimal outcomes, we must go beyond the code. Genetics provides context, but function lies in expression, interaction, and adaptation. That’s where the clinical effort—and therapeutic innovation—must be focused