Speaking Frankly: Sanger’s legacy

Editor’s note: Frank Leibfarth is a postdoc who is trying to make his way through the academic maze. Find him contributing to the Sceptical Chymist or continue the conversation on Twitter @Frank_Leibfarth.

– – – – – – – – – – – – – – – – – – –

Frederick Sanger, the British biochemist and two-time Nobel laureate, died this week at the age of 95. He holds the distinction of being the only individual to win two Nobel Prizes in Chemistry and one of only four people to win two Nobel prizes in any field; an honour he shares with John Bardeen, Marie Curie, and Linus Pauling.

Sanger took a fundamentally chemical approach to solve complex problems in molecular biology and genetics. Early on he became interested in the structure and sequence of biopolymers, which led him to study and eventually fully sequence the protein insulin. This feat of ingenuity, chemistry, and spectroscopy led to his first Nobel Prize awarded in 1958. Soon after, he moved from the University of Cambridge to the British Medical Research Council Laboratory of Molecular Biology, where he studied with a slew of young, ambitious, and talented scientists including the likes of Max Perutz and Francis Crick.

Here, Sanger began his work on developing a method to sequence deoxyribonucleic acid, or DNA, the alphabet of heredity. His success in this field, culminating in the development of the ‘Sanger method’ for sequencing DNA, was one of the most important scientific feats of the last century. Originally employed for sequencing the complete genome of a virus and then human mitochondria, the Sanger method would eventually be the primary technology used to complete the sequencing of the entire human genome. Sanger shared his second Nobel Prize in 1980 for his work on sequencing DNA, only three years before his retirement from scientific research in 1983.

Sanger’s legacy will not be one of excess. Despite his groundbreaking contributions, he only published around 100 research articles. The quality of his work is undeniable; each of his publications has been cited an average of almost 1000 times. A commentary penned by Sanger in 2001 provides a rare glimpse into his research philosophies. He worked at the bench throughout his career, preferring to do experiments himself than plan them for others. Furthermore, he mentions the importance of interacting with scientists outside his discipline, “who were interested not only in what they were doing but also in other people’s work and keen to exchange ideas.”

Although Sanger won awards for his landmark discoveries, an underappreciated facet of his contributions was the technology he created to make these discoveries possible. He was primarily interested in developing simple, scalable, and reproducible chemical techniques to sequence these biopolymers. As a result, Sanger’s legacy extends far beyond the sequencing of the amino acids in insulin or the genetic code of mitochondria. His user-friendly methods have been adopted by scientists around the globe and are indirectly responsible for much of our advances in modern medicine.

Sanger’s scientific career ended more than three decades ago, but in many ways he is a model for the next generation of chemists. The day-to-day work in his lab consisted of fundamental chemical investigations of the structure of biopolymers; breaking them down, reconstructing them, and developing analytical methods to see how and where bonds broke and reformed. From a broader perspective, however, Sanger can be rightfully credited with being a founding member of the fields of molecular biology and genetics, a seemingly far cry from ‘traditional’ chemical disciplines. So while some would argue that chemistry is a mature discipline, I contend that well-trained chemists are only scratching the surface of their potential.

There are surely many grand challenges within the discipline, but chemists are broadly trained to be able to make molecules, understand their bonding properties, and connect their structure to function. If elucidating the primary structure of proteins and DNA revolutionized biochemistry in the 20th century, could understanding the structure, interactions, and dynamics of the cell membrane or extracellular matrix do the same in the 21st century? Problems of structure and bonding will always require the skills of a chemist to solve and Sanger recognized that in the 1940s. He has shown us the roadmap, now we only have to follow it.