The Origins of Pharmacogenomics With John J. Miller, MD

In a new educational series on psychiatric pharmacogenomics, John Miller, MD, provided a broad historical and scientific framework for understanding how genetics informs psychopharmacologic practice.

Miller traced the origins of hereditary theory from Hippocrates through Gregor Mendel's landmark pea experiments in the 1860s, which established foundational principles of dominant and recessive inheritance. He highlighted the work of Rosalind Franklin and Watson and Crick, describing the double helix structure of DNA as a pivotal moment, noting it provided "a cohesive model for understanding how deoxyribonucleic acid created a 3-dimensional double helix that allowed the transmission of genetic information."¹ The sequencing of the human genome's 3 billion base pairs was completed in rough draft form in 2001, and by 2004, the first pharmacogenomic clinical device received approval, offering data on 2 cytochrome P450 genes relevant to medication metabolism.

Miller emphasized that pharmacogenomic research expanded dramatically by 2010, growing from fewer than 100 publications annually to thousands.² He distinguished psychiatric pharmacogenomics as a specialty-specific domain, noting that while a large body of genomic knowledge exists, only a subset has crossed the threshold of clinical actionability. He stated that in psychiatry, clinicians must focus on genes that have been "published, reinforced in our organizations that vet when a gene has crossed the clinical threshold of being clinically actionable to actually use in our decision-making in medicine."

Miller concluded with a review of cellular biology, explaining how DNA transcription and translation produce the protein products—including drug-metabolizing enzymes and receptors—that underlie pharmacogenomic variability.

Dr Miller is Medical Director, Brain Health, Exeter, New Hampshire; Editor in Chief, Psychiatric Times; Volunteer Consulting Psychiatrist, Seacoast Mental Health Center, Exeter; Consulting Psychiatrist, Insight Meditation Society, Barre, Massachusetts.

References

1. The history of DNA timeline. DNA Worldwide Group. Accessed April 6, 2026. https://www.dna-worldwide.com/resource/160/history-dna-timeline

2. Rackow AR, Snyder I, Stevenson JM, et al. Evaluation of the availability of clinical pharmacogenomics within the USA and utilization within an academic healthcare system. J Lab Prec Med. 2025;10.