I’m doubly appreciative of fireflies this year, as they’ve given us two fabulous gifts. One, the incredible gift of wonder. The other gift is a tiny molecule, precious and pragmatic.
Luciferase is a light-producing enzyme that was invented by fireflies. Over eons of evolution, it’s been fine-tuned to help fireflies find mates and avoid predators. And now this firefly enzyme has been harnessed by humans to help us fight against the global pandemic of COVID-19.
Surely it seems like magic, but firefly light comes from a carefully orchestrated chemical reaction that happens inside the firefly’s lantern. Luciferase hosts the party, inviting multiple guests (including ATP, oxygen, magnesium, and a much smaller molecule called luciferin), then sparking them to engage in a scintillating conversation that gets them excited enough to give off light.
Ever since its discovery in the late 1940s, firefly luciferase has been harnessed by scientists to improve human health. Early on it got used in food safety testing to detect good food gone bad – that is, food that’s been contaminated by microbes and so is unsafe for human consumption. To test meat, diary and soft drinks, kits made from firefly-derived chemicals would light up to show if a sample was contaminated with even tiny amounts of harmful bacteria. Similar kits were used by the pharmaceutical industry to measure cell viability when they tested anti-tumor drugs. Surprisingly, for over 30 years every smidgeon of luciferase that went into these kits came from wild fireflies harvested by collectors all across the U.S.
Each summer the Sigma Chemical Company recruited a small army of collectors that got paid ~50 cents per 100 fireflies; a $20 bonus awaited anyone who sent in 200,000 fireflies. All told, Sigma extracted luciferase from about 90 million wild-caught fireflies!! (Yes, I know it’s hard to believe. But you can find out more about bounty-hunting fireflies in Silent Sparks Chapter 8: Lights Out for Fireflies? or this story in Atlas Obscura). Quite fortunately for U.S. fireflies and their fans, in the 1990’s scientists finally decoded the DNA sequence that fireflies use to make luciferase. Using harmless bacteria as a bioproduction platform, synthetic luciferase soon became widely available.
Fireflies have enabled many advances in public health and medicine. Once the luciferase gene (this gene’s nickname is luc) was deciphered, the scientific and biomedical uses for firefly luciferase skyrocketed. Widely used as a genetic “reporter”, luc can be spliced together with any other target gene that scientists might want to study. Whenever the target gene gets activated, luc acts like a spy who reports back by emitting light, which can be quickly and easily measured using sensitive cameras.
Right now, firefly luc is helping us to understand and fight public enemy #1, the SARS-CoV-2 virus that’s responsible for the global pandemic of COVID-19.
A first step to conquering this deadly disease is understanding how the SARS-CoV-2 virus enters and replicates inside host cells. Researchers at Texas Medical Center have studied this process using pseudotyped viral particles. They grafted the S-protein from SARS-CoV-2 onto an innocuous virus, then added firefly luc as genetic reporter. When these pseudo-typed viruses attacked a cultured host cell, luc announced the attack loud and clear: the replicating virus particles emitted light, which could be measured very accurately to determine virus replication rates.
In a completely different application, a research team in Japan has combined luciferase with a fluorescent protein to invent a very sensitive antibody test. Their test quickly detects multiple antibodies using just a tiny drop of blood, and the results are read using a smartphone app. As scientists race to figure out how to treat and prevent COVID-19, it seems that fireflies may help us win this fight.
These beloved insects have given us so much – the gift of wonder + the gift of light. We owe them a huge debt of gratitude, so the least we can do is preserve them for future generations to enjoy. And who knows what other chemical riches lie waiting to be discovered within the firefly pharmacopiea?