Negative Consequences of the Central Dogma

The oversimplification of the Central Dogma has resulted in the long-term neglect of essential elements of all organisms. Even as an undergraduate, I recoiled at the concept of the Central Dogma, which was considered so important as to appear on our essay-based exams in Biochemistry and Molecular Biology. Although the Central Dogma, put forth by Francis Crick,¹ is not as simplistic as “DNA begets RNA which begets proteins,” this simplification has steered molecular biology away from placing equal emphasis on proteoglycans and lipids, and has emphasized a nucleic acid–centric approach to biology.

The limitation of the Central Dogma is not that it is wrong, but rather the dogma limits our minds. The entire focus of Crick’s statements was on the transmission of information. However, the transmission of information explains nothing beyond those limited goals, albeit essential, but limits our horizons in appreciating not only the complex functions and activities of cells but also the interactions—dynamic as they are—in multicellular organisms.

The net result of the emphasis on the Central Dogma has been a pervasive focus on nucleic acids and proteins, with the demotion of lipids, carbohydrates, proteoglycans, and preponderance of cellular and intercellular processes. There has been so much knowledge to obtain, and remaining substantial knowledge to gain, that the combination of the Central Dogma and the easy tools of nucleic acid chemistry has driven our focus down a narrow road. I had the privilege of Christian Anfinsen teaching me protein chemistry. During his lecture on protein sequencing, he commented that although he was teaching it, the knowledge had no practical use as DNA sequencing had made the technique obsolete. His statement, which I rejected then, almost as a dare, was in many ways a lament about the “molecular biology revolution” (really the nucleic acids revolution) that was being ignited by PCR.^2,3

Fundamentally, the Central Dogma does not go far enough. DNA begets RNA, which begets proteins. The encoded information is sufficient to enable the processes required to create a cell and all the processes required for the replication of the cell, as well as a multicellular organism. In truth, when Crick formulated the Central Dogma, he was not thinking about these processes; his meaning was transmission of information, sufficient to replicate a cell, not how the information is transformed into the diversity of biological process.⁴

As our tools and knowledge of the biochemistry of nucleic acids have expanded, the breadth of research on proteins has expanded. Now is the time to expand our energies devoted to exploring the complexity of the biology in fields of lipids and proteoglycans biology and fully appreciate the cell based on the diversity of its essential biochemical constituents.