Fang Fude of Peking Union Medical College Outlines Two Strategic Goals of U.S. Precision Medicine

On July 24, the Second Precision Medicine and Gene Sequencing Conference was held at the Peking Union Medical College Academic Auditorium in Beijing. Fang Fude, a researcher at the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, delivered a keynote speech titled “Strategic Reflections on Precision Medicine: My Understanding of Precision Medicine.” Below are the speaker’s insights compiled by VCBeat.

Genomics, genomic biology, and disease and health constitute the most fundamental framework of precision medicine biology. From an academic perspective, genomics primarily addresses issues related to genome structure and genetic information; precision biology focuses mainly on function and mechanisms; and the states of disease or health primarily concern phenotypic issues. There exists an intrinsic connection and correspondence between specific molecular biological structures and functions and specific phenotypes (whether healthy or diseased).

The fundamental task of precision medicine is to determine the correspondence between molecular subtypes and health or disease phenotypes. Complex trait diseases (chronic diseases) involve phenotypic diversity, which leads to molecular heterogeneity; this constitutes the primary focus of precision medicine research. The core issue in precision medicine is molecular stratification.

The United States primarily focuses on genomics and the relationship between disease and health. The strategic intent of the U.S. Precision Medicine Initiative is clearly defined, with two main objectives: first, to construct a map linking genotypes to disease phenotypes; and second, to achieve a paradigm shift in medical genetics theory.

Construction of a Genotype-Disease Phenotype Relationship Graph

Molecular subtyping involves genomic sequencing of millions of individuals to construct a map delineating the relationships among genotypes, haplotypes, genomic profiles, and phenotypes. The ultimate goal is to leverage this relational map to establish a new diagnostic and therapeutic framework that, in addition to disease diagnosis and treatment, includes assessment of individual health status and identification of optimal timing for interventions, thereby achieving the objectives of disease prevention and health preservation. This approach embodies not only the treatment of diseases but also the strategic intent of safeguarding public health through proactive intervention. With clearly defined genetic information and a well-understood genetic background, precision medicine for diseases adheres to the “Four Principles”: personalization, minimization, simplification, and staging. In contrast, precision medicine in the United States has relatively limited goals and target populations; although it covers a diverse range of diseases, it selectively focuses on specific cases.

Achieving the Transformation of Medical Genetics Theory

For a long time, genetic research in medicine, particularly on complex diseases, has been primarily guided by the Mendelian theory (phonetic translation), which is inadequate for addressing complex diseases. Past genetic analyses, including gene sequencing and genome-wide scans, were conducted under the framework of Mendelian theory and yielded limited effectiveness. Therefore, a theoretical paradigm shift is necessary. The “rare variation–common disease” hypothesis was subsequently proposed, suggesting that mutations may arise due to environmental factors. Previously, it was not feasible to construct such a theoretical framework; however, with the advent of next-generation sequencing and deep sequencing technologies, it is now possible to establish this theoretical system. A successful transition in this theoretical paradigm would represent a significant breakthrough, providing substantial theoretical support for guiding research on complex diseases.

The foundation of precision medicine in the United States is also big data, which relies on genetic resources, technological platforms, bioinformatics, and other supporting conditions. In addition to diagnosis, prevention, treatment, and prognosis of diseases, future development will shift toward health maintenance. Therefore, some predict that over time, the current hospital models will gradually diminish, while health clinics and hospitals specializing in health consultations will become the primary medical institutions. This represents a relatively forward-looking perspective. Precision medicine in the U.S. involves not only sequencing but also complementary research. The main focus of U.S. precision medicine research is to identify causal variants—pathogenic mutations. To achieve this goal, two major tasks are required: first, more work related to single nucleotide polymorphisms (SNPs); second, in-depth exploration of genetic information to uncover additional data supporting this objective. Once causal variants are identified, there are two subsequent pathways: one is to further elucidate their functions and mechanisms, and the other is to translate these findings into clinical applications.