Frederick Sanger never meant to study insulin; he was simply in the right place at the right time.
Born in Gloucestershire, UK in 1918, Frederick Sanger was the son of a medical practitioner. Influenced by his father and older brother, Sanger quickly developed an interest in biology and respect for the scientific method. Originally intending to study medicine, he switched to science to “concentrate [his] activities and interests more on a single goal.” A student at the University of Cambridge, he developed a keen interest in biochemistry and as a conscientious objector during the war, was permitted to study for a PhD. Receiving no stipend, he was largely able to support himself as his mother was the daughter of a relatively wealthy cotton manufacturer.
In 1943, having just completed his doctorate in Biochemistry, a 25-year-old Sanger joined the lab of Dr. A.C. Chibnall at the University of Cambridge. The lab’s focus was to determine the makeup of protein molecules, what is referred to as its sequence. Sanger worked with the understanding that proteins are made of a combination of twenty building blocks, called amino acids, each tethered to one another like train compartments. However, Sanger wanted to discern whether each kind of protein had a unique sequence, like how our names are unique and always spelt the same way. To prove this, he needed to show that at least one protein had a set sequence. The ideal protein for study would have to be available in high purity and be relevant medically. Enter insulin, the protein selected for the project, and so began Sanger’s 12-year journey into deciphering the sequence of the first protein ever.
Sanger’s research encountered obstacles on many fronts, as is often the case with highly novel research. To determine the combination of amino acids that make up insulin, Sanger had to break the protein apart into small fragments. The ingenuity of his methods came into play here, using molecular scissors known to cut proteins at very specific sites. With a variety of these ‘scissors’, or enzymes as they’re called, he created insulin fragments of differing composition and lengths. From there it was like a puzzle, where you have short snippets of letters and words, some of which overlap, and you have to piece them together to recreate the full paragraph. Compared to English letters and words, it is much more difficult to construct protein sequences, because the snippets take a great deal of work to produce, and you can’t tell if the sequences make sense when aligned the way our words and sentences do.
Sanger’s gargantuan undertaking, the sequencing of insulin, succeeded in 1955. He demonstrated by way of insulin that proteins are indeed made of very specific sequences of amino acids. This finding shifted the paradigm on protein composition, and informed research for decades to come on how a protein’s sequence affects its shape, and ultimately its function.
This breakthrough marked the end of Sanger’s chapter with insulin and diabetes research, earning him a Nobel Prize in Chemistry in 1958. From here he pursued sequence analysis from other molecules, RNA at first, then later DNA. The advent of DNA sequencing garnered Sanger a second Nobel Prize in 1980, marking him only the fourth person to ever win two Nobel Prizes. Throughout, Sanger was always keen to highlight that his achievements were far from single-handed. He owed much of it to his collaborators, mainly students and postdoctoral fellows spending a few years in the lab and bringing their experience and ideas with him. He also credits much of his success to his wife, Margaret Joan Howe, for providing “a peaceful and happy home.”
A few years later, Sanger retired and shifted his attention to his family and favourite hobbies: gardening and what he describes as “messing about in boats.” A modest and courteous man, he declined the honour of knighthood as he did not want to differentiate himself from others through the epithet “Sir”. Having enjoyed thirty years of retirement, Sanger quietly passed away in 2013.
— Written by Annoj Thavalingam