By Kevin Davies, PhD
WASHINGTON DC—Brendan Lee, MD, PhD, the president of the American Society of Human Genetics (ASHG), reflected on decades of progress in genetics research and therapies in his presidential address on Wednesday, marking the Society’s 75th anniversary annual convention.
Lee is the Robert and Janice McNair Endowed Chair and professor of molecular and human genetics at Baylor College of Medicine in Houston, TX.
Lee’s personal journey included the story of chain migration, arriving in the United States as an immigrant, settling in Houston 30 years ago, where he took his pediatrics/genetics training. He cut his teeth learning Sanger sequencing, applied to the study of skeletal genetic disorders including dwarfism and Marfan syndrome.
Lee began his speech by assuring the audience that his talk was prepared with “no use of ChatGPT” or any other generative AI tools. Embracing the meeting’s overall theme—One humanity, many genomes—Lee reflected on the remarkable progress the field has made.
Human beings share 99.9% of their genome sequence. But as a medical geneticist, Lee said, “that small portion of difference can have a profound impact.” With the arrival of DNA microarrays, Lee and his colleagues were able to study common variants in common phenotypes. As genomic technology advanced rapidly, that evolved to the dissection of rare variants in common phenotypes.
Today, Lee said, “therapy for genetic disease has become a clinical reality.” There are now more than 30 gene and cell therapies for genetic diseases and cancer.
Lee said the milestones celebrated by ASHG mirror his own journey and beyond. Since the birth of the Society, genetics science has been highlighted by:
- DNA and the human genome (the double helix, recombinant DNA, Sanger sequencing, gene mapping, the Human Genome Project, next-generation sequencing, and the newly complete reference genome)
- Variation in the human genome (single nucleotide polymorphisms, haplotypes, the 1000 Genomes Project, reference population databases)
- Genetic basis of disease
- Genomic medicine (impact on healthcare)
- Genome function beyond DNA (epigenetics and gene expression)
“Humans are now the best model for discovery of human genetic variation,” Lee said, citing resources such as the NIH Undiagnosed Diseases Network. Progress in medical diagnostics includes whole genome sequencing, cell-free DNA, the promise of polygenic risk scores, clinical transcriptome analysis and clinical metabolomics. Gene therapy has moved in many exciting directions, including mRNA and oligonucleotide therapy, and CRISPR, with major advances in retinitis pigmentosa, spinal muscular atrophy, Duchenne muscular dystrophy, hereditary amyloidosis, and as signaled by this week’s FDA AdCom meeting, sickle cell disease.
The growing diversity of patients, study participants and the genetics workforce is another welcome development, Lee said, noting programs such as All of Us and H3Africa. But he cautioned that there are also emerging threats, notably the “growing voice of ‘anti-science’.”
“We must engage on this issue as citizen scientists,” said Lee.
Lee wrapped up his speech by looking forward to the next wave of future milestones. These include:
- The equitable expansion of precision medicine, including diagnosis for every genetic disease, and the application of targeted treatments for all; and the Integration of genomic information to inform health care and prevention for all
- Increase diversity of genomics research, including equitable representation and longitudinal biobanks
- New avenues for research, including new approaches to treat and test the efficacy of treatments, and
- Increased awareness of genetics
The ASHG conference runs from November 1–5 in Washington, D.C.