An interesting path has led me to co-author Arctic Signal.

After graduating in Natural Sciences from the University of Cambridge in 2010 I worked as a research scientist at Cambridge. I gained advanced experience in cloning genes in bacteria and yeast cells techniques, protein expression and purification, and DNA sequencing techniques ion-exchange chromatography. In another position in Cambridge, I assisted in identifying genes responsible for a form of glucose use and regulation

During this period I began to search the medical literature for reports on communities that had maintained zero-carb diets, including case reports for what was then known as the L479 genetic mutation – what would later become known as the Arctic Variant and likely the swiftest genetic mutation to become dominant in its host community in global history.

In 2012, the mutation was only vaguely understood in relation to its host populations living in Canada. There was little global knowledge of its historical and geographical occurrence, nor the reason for its ancient selection. However, as I discovered, initial reports about the mutation suggested that its carriers were somehow prevented from entering a state of chronic ketogenic fat burning, even when they fasted or avoided all glucose, which was usually thought to promote ketogenic fat burning.

A lucky aspect of the sequencing of the first ever ancient DNA sample in 2010 finally convinced me to collaborate more closely with my writing partner to understand the history and biological meaning of what we viewed as the most dramatic mutation in human history.

That famous 4,000-year-old sample from a “Saqqaq” man in Greenland derived from a ball of permafrost-frozen hair wrapped around a whalebone comb. This individual was part of what many scholars now recognize as the Arctic Small Tool Tradition. This culture emerged among the ancient ancestors of the Inuit people in the circumpolar Arctic region. The sample was indeed the closest DNA proxy for the ancient Inuit people of Arctic North America, who had made their way to Greenland from 6,000 to 4,000 years ago.

But it took four years to discover that the mutation that came to be known as the Arctic Variant appeared in that first ancient DNA sequence. In 2014, a team of scientists worked out that the DNA sequence obtained from the 4,000-year-old Saqqaq man also incorporated the oldest known example of a new variant, or allele, linked to the “CPT1a L479” mutation on its respective chromosome. This mysterious “anti-ketogenic” mutation, researchers noted, was especially prevalent among groups that stayed in the area between Northeast Asia and Greenland, setting them apart from other Indigenous populations that came to the Americas much earlier through different paths. Consequently, this variant is absent in samples from ancient or modern Indigenous communities located south of the Arctic region.

With the discovery of the mutation in the ancient Greenland sample, scientists worldwide began to ask a question that we had already started considering: why would a mutation arise that reduces ketogenic fat burning in a zero-carb environment like the Arctic, where glucose-rich grains, tubers, and plants were absent, and where fat would typically serve as an alternative fuel source?

The urgency of that question cemented mydecision to leave British laboratories. In late 2014, I moved permanently to America to access materials and research groups – free from formal laboratory commitments to concentrate on this global conundrum and to collaborate with Gideon.

My 2020 peer-reviewed article for Molecular Genetics and Metabolism is titled: “Inuit metabolism revisited: what drove the selective sweep of CPT1a L479?” The hypothesis in that article provides the bridge to Arctic Signal.