Future of Medicine: Genomics and Precision Medicine Explained

Genomics has gone from a single international research project to a routine tool in oncology, rare disease and, increasingly, drug prescribing. At the same time, the first genome-editing therapies have reached patients.

From one genome to routine testing

The Human Genome Project was an international effort, completed in 2003, that produced a reference sequence of the human genome. That reference still had gaps in repetitive regions that were technically hard to sequence.

In 2022, the Telomere-to-Telomere consortium published the first complete sequence of a human genome, closing those gaps. Completing the reference matters for clinical genomics because some disease-relevant variation lies in previously unresolved regions.

The other change is cost. The cost of sequencing a human genome has fallen far faster than would be expected from improvements in computing alone. Exact prices depend on technology, scale and what is included (sequencing only versus interpretation and reporting).

What precision medicine means

Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment and lifestyle for each person. Genomics is a key component, but precision medicine also uses biomarkers, imaging, clinical data and social determinants.

Where genomics already changes care

National genomic services

The NHS Genomic Medicine Service in England aims to provide consistent and equitable access to genomic testing, with a national test directory specifying which tests are available and for which patients. This is one model of how health systems bring genomics into mainstream care: a defined menu of tests, regional laboratory hubs and clinical pathways that tell non-geneticists when to order.

In the United States, NIH's All of Us Research Program is building a large, diverse research cohort that combines genomic, health record, survey and wearable data. One explicit goal is to include groups historically under-represented in biomedical research, which matters because genomic reference data have been skewed toward people of European ancestry.

Genome editing reaches patients

In December 2023 the FDA approved two gene therapies for sickle cell disease, including Casgevy, the first FDA-approved treatment using CRISPR/Cas9 genome editing. Casgevy is approved for patients 12 years and older with sickle cell disease and recurrent vaso-occlusive crises. The treatment involves collecting the patient's own blood stem cells, editing them, and returning them after myeloablative conditioning.

This approval matters for three reasons:

• It shows that genome editing can pass full regulatory review.
• It highlights the practical complexity: specialised centres, conditioning chemotherapy and long follow-up.
• It raises questions about cost and global access, since sickle cell disease is most common in regions with limited health budgets.

The hard problems

Variant interpretation

Sequencing finds many variants; deciding which are pathogenic is the difficult part. Results are often reported in categories such as pathogenic, likely pathogenic, variant of uncertain significance (VUS), likely benign and benign. A VUS is not a diagnosis and should not drive major decisions on its own, but it can be reclassified as evidence grows.

Ancestry bias

When reference databases under-represent some populations, variants in those groups are more often classified as uncertain, and polygenic risk scores may perform worse. Initiatives like All of Us aim to correct this.

Consent, privacy and incidental findings

Genome sequencing can reveal findings unrelated to the original question, including risks for relatives. Consent processes must explain what will and will not be reported, how data will be stored and whether it may be used for research.

Equity and cost

Advanced therapies and broad sequencing are expensive. Without deliberate policy, precision medicine could widen gaps between and within countries.

What clinicians need to know

Most clinicians will not run a genetics lab, but nearly all will meet genomic results. Core competencies include:

1. Knowing when to test. Recognise red flags for inherited disease, such as early-onset cancer, multiple affected relatives or unexplained developmental disorders.
2. Choosing the right test. Single gene, panel, exome or genome, and germline versus tumour testing.
3. Reading the report. Understand variant classes, penetrance and what "no pathogenic variant found" does and does not exclude.
4. Communicating results. Explain uncertainty, implications for family members and next steps.
5. Referring appropriately. Involve clinical genetics and genetic counsellors for complex cases.
6. Acting on pharmacogenomic results. Use guideline-based recommendations where a result affects drug choice or dose.

Common mistakes

• Treating a VUS as pathogenic.
• Assuming a negative panel rules out all genetic causes.
• Forgetting cascade testing for relatives.
• Ordering tumour-only testing when germline testing is also indicated.

How genomics connects with AI and digital health

Genomic data are large and complex, so AI tools are increasingly used for variant prioritisation, image-based phenotype matching and integrating genomic with clinical data. The same validation and bias concerns discussed in AI in diagnostics apply. Combining genomics with wearable and health record data, as All of Us does, links precision medicine with digital health and wearables.

What students should study now

Genetics questions in licensing exams increasingly go beyond inheritance patterns to test interpretation and clinical application:

• Modes of inheritance, penetrance and expressivity.
• Molecular basis of key disorders such as haemoglobinopathies, cystic fibrosis and hereditary cancer syndromes.
• Principles of genetic testing, consent and counselling.
• Pharmacogenomic examples that appear in pharmacology.

You can practise these topics with exam-style vignettes in the MediFlow app, alongside the rest of the basic and clinical sciences.

A worked example: a family history of early bowel cancer

Consider a 35-year-old whose father and aunt were diagnosed with bowel cancer in their forties. A genomics-literate clinician would:

1. Take a three-generation family history, including cancer types and ages at diagnosis.
2. Recognise the pattern that suggests a possible inherited cancer syndrome rather than chance.
3. Check whether an affected relative has already been tested, because testing an affected person first is often more informative.
4. Follow the local pathway, such as the national test directory used by the NHS Genomic Medicine Service, to decide which test is available and who should order it.
5. Explain possible results in advance: a pathogenic variant, no variant found, or a variant of uncertain significance, and what each would mean for screening.
6. Plan for relatives, since a confirmed pathogenic variant allows targeted testing of other family members.

This example shows why genomics is becoming everyone's business. The clinician who first hears the family history is rarely a geneticist.

Questions to ask about any new genomic test

• What clinical question does it answer, and would the result change management?
• Is it a germline or a somatic test, and is that the right one?
• How are variants classified, and how will reclassification be communicated?
• What incidental findings might arise, and has the patient consented to receive them?
• Is the test validated in people of the patient's ancestry?
• Who pays, and is it part of an approved national or insurer pathway?

Outlook

The next decade of genomic medicine will likely bring broader use of genome sequencing in diagnosis, more pharmacogenomic testing at the point of prescribing, additional gene-editing therapies, and more diverse reference data. The bottleneck is shifting from generating data to interpreting it, communicating it and paying for what it reveals. Clinicians who are comfortable with that interpretation will be central to precision medicine.

Continue the series with how medical jobs will change.