There are approximately 10,000 inherited diseases. These diseases impact nearly a billion people globally. Many of these are considered rare or orphan diseases as they affect fewer than 100,000 people. While others, such as Parkinson’s and Alzheimer’s disease, are household names, these diseases together form a class that has proven intractable. They have in common a gene or set of genes that are passed through families and flow across continents, impacting new populations with each crossing.

In the last decade, methods such as CRISPR have been developed to correct such genes to cure or prevent diseases. However, identifying the location of these disease-causing genes remains a challenge, and there is currently no universal or standard approach to enable gene therapies. Development of such an approach will have an immediate and significant impact on global health. There are candidate approaches that have been validated in model organisms. One such approach makes use of population variation wherein genome datasets from various heritages are interrogated to triangulate the specific location of disease-causing genes. Translating this approach to humans is promising but highlights implicit systemic biases within public and private international efforts to collect human genomes. Emblematic of this is the human genome reference, advertised as representing all humans, is largely from only one male in New York, USA. Another issue is the sheer amount of data contained in human genomes needed to power population variation. New models of generative AI would be required to be able to encompass the large dimensional space.

I propose exploration and examination of candidate approaches such as population variation that may ‘solve’ inherited diseases. What are the various pitfalls to overcome? As I have highlighted, these range from scientific to computational to political. And lastly, what benefits will be had if successful? For instance, can we replicate the revolution in the quality of human life that was brought about by antibiotics and vaccines in the 20th century?